- Email: [email protected]
A gap type RF induction heating system for ferromagnetic hyperthermia
Proceedingsof the 33rd Annual ASTRO Meeting
117
ulceration, in patients Eollowed at least 1 month, and surgical repair (muscle flap, 8 fields; skin graft, 3 fields) were related to .:he total PT dose (previous RT & present RT). The median total dose for those needing surgical repair or with persistent ulceration was 8640 cGy and 8050 cGy, respectively, compared to 6600 CGY for those in both (IJZOUPSwho did not. TWO of these muscle flaw (one in each CI=OUD _ _ below). however; wefe planned prior to treatment and were not undertaken because of ulceration. Medial RT Ave. Max. Dose (cGy) Tumor Temp DeliveredPFirstTx 6220 44.6OC 44.eoc 3200
Second/Third Persistent Acute Degree Burn (>l mo jj TX) Surgical Ulcerationor NO 7/14(50%) 2/16(13%) g/16(56%) 2/14(14%) 2/17(12%) Yes 11/20(55%) 9/22(41%) 19/22(86%) 13/20(65%) 9/22(41%) p=.os p=.o37 p=.oo4 p=.o4 CONCLUSION: We conclude that the combination of RT, HT and of CT may be more toxic than treatment with HT and RT alone, especially in patients who have been treated with prior RT. The impact of CT on the therapeutic index of HT and RT remains to be determined. Complete
9 THERMOSENSITIZATION
OF TUMORS BY LOWERING THE INTRACELLULAR pH
Chang
C. Lyons, Seymour H. Levitt and Brian ROSS*
W. Song,
John
University of Minnesota Medical School, Dept. of Therapeutic Radiology, Harvard St. at East River Road, Box 494 UMHC, Minneapolis, MN 55455; *University of Michigan, Dept. of Radiology, Kresge 3 Research Building, Box 0553, Ann Arbor, MI 48109 We have oreviouslv observed that amiloride, a diuretic drug and an inhibitor of Na+/H+ Puroose: antipot-< through the cell membrane, could significantly lower the pHi of tumor cells in vitro, and that whereas DIDS, an inhibitor of HC03-/Cl' exchange, alone could not lower the pHi, it increased the effect of amiloride in reducing the pHi. We also observed that the thermosensitivity of the tumor cells in vitro could be siqnificantlv enhanced by amiloride alone or in combination with DIDS in acidic medium, e.g. pH 6.6. The purpose of thi; study was to investigate the effects of amiloride and DIDS alone or in combination on the thermoresponse of tumors in vivo. Materials and varigus amounts of 43.5 C water for 1 diameters. A group
A/J mice bearing 6-7 nun SCK tumors in the hind leg were injected i.p. with Methods: amiloride and DIDS alone or in combination, the tumors were then heated 1 hr. later with hr., and the changes in the growth rate of tumors were determined by measuring the tumor of tumors were heated without prior treatment with the drugs.
The volurie of untrea&ed control tumors increased 4 times in 4.2 + 0.3 days and the volume of Results: tumors which received heating (43.5 C for 1 hr.) alone increased 4 times in 7.7+ 0.4 days. When the host mice were injected i.p. with amiloride at 10 mg/kg and the tumors were heated 1 h?. later, the tumor volume increased 4 times in 9.7 + 0.4 days, which was about 2 days longer than that of tumors treated with heating A similar delay in tumor growth was observed when the mice were injected i.p. with 25 mg/kg of DIDS alone. When 10 mg/kg of amiloride and 25 mg/kg of DIDS were injected i.p. and the tumors and heated 1 hr. later. were heated 1 hr. later, the tumor volume increased 4 times in 12.0 + 0.6 days, which was significantly longer than that after lheating alone (7.7 + 0.4 days) and that of untreayed control tumors (4.2 + 0.3 days). The study with p-31 NMR spectroscopy indiczted that the content of ASP in the tumors significantly decreased by heating and that the ATP content was further reduced when the host mice were treated with amiloride prior to heating the tumors. The results of the present study strongly suggest that it is feasible to increase the Conclusion: thermosensitivity of tumors using drugs such as amiloride which lower the intracellular pH. The effects of these drugs are more pronounced in an acidic environment than in a neutral or alkaline environment and thus the tumors may be preferentially thermosensitized by these drugs. (This work was supported NC1 grant number CA13353 and grant number PDT-209 from the American Cancer Society.)
10 A GAP TYPE K.Ohura,
RF
INDUCTION
Y.Kotoura,
of **rDep. Sumitomo
Orthop. Metal
HEATING
T.Yamamuro, and Ind.,
*Radial., Ltd.
SYSTEM
FOR FERRUvQXXETIC
M.Hiraoka*, and
**Inst.
M.Abe*,
HYPEF3HEZRMIA
T.Kokubo**,
for Chem.
Res.,
Purpose:Various heating methods have been developed for still difficult to heat deep-seated tumors. One promising problem is the implantation of ferromagnetic thermoseeds alternating magnetic field. We report the performance of a new induction heating heating experiments with ferromagnetic thermoseeds.
M.Yamashita***, Kyoto
Univ.,
Y.Ebisawa*** Japan.
hyperthermia. However, technique for solving which generate heat system
and
the
results
it
is this in an of
118
RadiationOncobx
Biology, Physics Volume 21, Supplement1
Materials & Methods:This heating system generates a 100 kHz magnetic field inside the gap of a C-type troidal core (cross section : 10 x 10 cm, gap width : lo-25 cm) and automatically controls the field strength according to the temperature of a sensor. The magnetic field profile was mapped utilizing a search coil. VX2 tumor of rabbit was heated by an array of Fe-Pt thermoseeds. Rabbit tibia1 bone with bone tumor was heated by a intramedullary implanted pin made of a ferromagnetic glass-ceramic. Results:The obtained magnetic field strength perpendicular to the axis of the troidal core was uniform inside the core gap. The field sharply attenuated outside the core edge. The maximum field strength at the gap center when gap width was 25 and 10 cm, and at the gap end was 100, 200 and 300-Oe, respectively. Fe-Pt thermoseeds inserted perpendicularly to the skin heated the tumor fairly homogeneously without the automatic reguration. An intramedullar ceramic pin heated the whole bone to 42 ‘C. strong and confined field is Generating an uniform. needed to achieve the temperature homogeneity and’sufficient temperature rise, and to avoid direct tissue In every respect, this heating system is heating. supposed to be superior to the other induction heating system. Conclusion:The new induction heating system generated an uniform and strong magnetic field confined inside the core gap, and effectively heated experimental soft tissue and bone tumors.
11 ANALYSIS OF TEMPERATURE DISTRIBUTIONS OF INTERSTITIAL HYPERTHERMIA USING A HOT WATER SYSTEM. G. Stuecklschweiger, Ph.D.*, K. Arian-Schad, M.D.*, D.S. Kapp, Ph.D., M.D.+, L. Handl-Zeller, M.D.*, and A. Hackl, M.D.* *University Clinic of Radiology, Department of Radiation Therapy, Graz, Austria +Department of Radiation Oncology, Stanford University, Stanford, California, 94305
Purpose: Interstitial hyperthermia (IHT) is being increasingly employed as an adjunct to brachytherapy in the treatment of implantable tumors. Of the several IHT systems available, perhaps the simplest to use are the circulating hot water systems. In clinical trials employing radiation and hyperthermia, thermal parameters, including mean minimal intratumoral temperature, have correlated with clinical outcome. An analysis was therefore undertaken of the thermal distributions obtained during our initial experience with IHT employing steel needles and the KHS9 hot water IHT system. Materials 81Methods: Twenty patients (12 with anal cancers, 5 with recurrent gynecological tumors, and 3 with metastatic melanomas) received a total of 29 IHT treatments in combination with brachytherapy. The IHT goal was to maintain intratumoral temperatures of 42.5% for 40 minutes. Temperatures were monitored by repetitively manually mapping 3-point thermocouple probes at 0.5 cm intervals within one or more hollow needles placed transtumorally for thermometry purposes. The temperature of the water inside the controlled temperature waterbath (Tw), the inflow water temperature (Tin), the outflow watertemperature (Tout), and the intratumoral temperatures were recorded at intervals of 5 seconds. The time to obtain steady-state temperatures and the thermal washout rates were also determined. The intratumoral thermal distributions were characterize-he mean minimum temperature (m), the mean average temperature (G) and the mean maximum temperature (Tmax) for all IHT treatments and for all IHT treatments for each of the three different tumor types. Results: To achieve the desired intratumoral temperatures, maximum, average, and minimum Tw were 49.7%, 48.4%, and 46.2%, respectively. Steady-state intratumoral temperatures were reached in an average time of 4 minutes with a maximum time to steady-state of 6 minutes. For all treatments, the average difference of Tin and Tout was 0.2%. Tmin, Eand Tmax of all treatments were 40.8X, 42.8”C, and 45°C respectively. For the anal carcinomas, the values for these parameters were: 40.8%, 42.4X, 45.0%; for gynecological cancers: 41.0%, 43.2%, 43.9%; and for metastatic melanomas: 42.1%, 42.7’%, and 43.1 “C. Conclusion: The intratumoral thermal distributions obtained with this hot water system appear to be at least as good as those reported for other RF or microwave interstitial systems. This system is relatively inexpensive, simple to use, safe and requires no special treatment room.
117
ulceration, in patients Eollowed at least 1 month, and surgical repair (muscle flap, 8 fields; skin graft, 3 fields) were related to .:he total PT dose (previous RT & present RT). The median total dose for those needing surgical repair or with persistent ulceration was 8640 cGy and 8050 cGy, respectively, compared to 6600 CGY for those in both (IJZOUPSwho did not. TWO of these muscle flaw (one in each CI=OUD _ _ below). however; wefe planned prior to treatment and were not undertaken because of ulceration. Medial RT Ave. Max. Dose (cGy) Tumor Temp DeliveredPFirstTx 6220 44.6OC 44.eoc 3200
Second/Third Persistent Acute Degree Burn (>l mo jj TX) Surgical Ulcerationor NO 7/14(50%) 2/16(13%) g/16(56%) 2/14(14%) 2/17(12%) Yes 11/20(55%) 9/22(41%) 19/22(86%) 13/20(65%) 9/22(41%) p=.os p=.o37 p=.oo4 p=.o4 CONCLUSION: We conclude that the combination of RT, HT and of CT may be more toxic than treatment with HT and RT alone, especially in patients who have been treated with prior RT. The impact of CT on the therapeutic index of HT and RT remains to be determined. Complete
9 THERMOSENSITIZATION
OF TUMORS BY LOWERING THE INTRACELLULAR pH
Chang
C. Lyons, Seymour H. Levitt and Brian ROSS*
W. Song,
John
University of Minnesota Medical School, Dept. of Therapeutic Radiology, Harvard St. at East River Road, Box 494 UMHC, Minneapolis, MN 55455; *University of Michigan, Dept. of Radiology, Kresge 3 Research Building, Box 0553, Ann Arbor, MI 48109 We have oreviouslv observed that amiloride, a diuretic drug and an inhibitor of Na+/H+ Puroose: antipot-< through the cell membrane, could significantly lower the pHi of tumor cells in vitro, and that whereas DIDS, an inhibitor of HC03-/Cl' exchange, alone could not lower the pHi, it increased the effect of amiloride in reducing the pHi. We also observed that the thermosensitivity of the tumor cells in vitro could be siqnificantlv enhanced by amiloride alone or in combination with DIDS in acidic medium, e.g. pH 6.6. The purpose of thi; study was to investigate the effects of amiloride and DIDS alone or in combination on the thermoresponse of tumors in vivo. Materials and varigus amounts of 43.5 C water for 1 diameters. A group
A/J mice bearing 6-7 nun SCK tumors in the hind leg were injected i.p. with Methods: amiloride and DIDS alone or in combination, the tumors were then heated 1 hr. later with hr., and the changes in the growth rate of tumors were determined by measuring the tumor of tumors were heated without prior treatment with the drugs.
The volurie of untrea&ed control tumors increased 4 times in 4.2 + 0.3 days and the volume of Results: tumors which received heating (43.5 C for 1 hr.) alone increased 4 times in 7.7+ 0.4 days. When the host mice were injected i.p. with amiloride at 10 mg/kg and the tumors were heated 1 h?. later, the tumor volume increased 4 times in 9.7 + 0.4 days, which was about 2 days longer than that of tumors treated with heating A similar delay in tumor growth was observed when the mice were injected i.p. with 25 mg/kg of DIDS alone. When 10 mg/kg of amiloride and 25 mg/kg of DIDS were injected i.p. and the tumors and heated 1 hr. later. were heated 1 hr. later, the tumor volume increased 4 times in 12.0 + 0.6 days, which was significantly longer than that after lheating alone (7.7 + 0.4 days) and that of untreayed control tumors (4.2 + 0.3 days). The study with p-31 NMR spectroscopy indiczted that the content of ASP in the tumors significantly decreased by heating and that the ATP content was further reduced when the host mice were treated with amiloride prior to heating the tumors. The results of the present study strongly suggest that it is feasible to increase the Conclusion: thermosensitivity of tumors using drugs such as amiloride which lower the intracellular pH. The effects of these drugs are more pronounced in an acidic environment than in a neutral or alkaline environment and thus the tumors may be preferentially thermosensitized by these drugs. (This work was supported NC1 grant number CA13353 and grant number PDT-209 from the American Cancer Society.)
10 A GAP TYPE K.Ohura,
RF
INDUCTION
Y.Kotoura,
of **rDep. Sumitomo
Orthop. Metal
HEATING
T.Yamamuro, and Ind.,
*Radial., Ltd.
SYSTEM
FOR FERRUvQXXETIC
M.Hiraoka*, and
**Inst.
M.Abe*,
HYPEF3HEZRMIA
T.Kokubo**,
for Chem.
Res.,
Purpose:Various heating methods have been developed for still difficult to heat deep-seated tumors. One promising problem is the implantation of ferromagnetic thermoseeds alternating magnetic field. We report the performance of a new induction heating heating experiments with ferromagnetic thermoseeds.
M.Yamashita***, Kyoto
Univ.,
Y.Ebisawa*** Japan.
hyperthermia. However, technique for solving which generate heat system
and
the
results
it
is this in an of
118
RadiationOncobx
Biology, Physics Volume 21, Supplement1
Materials & Methods:This heating system generates a 100 kHz magnetic field inside the gap of a C-type troidal core (cross section : 10 x 10 cm, gap width : lo-25 cm) and automatically controls the field strength according to the temperature of a sensor. The magnetic field profile was mapped utilizing a search coil. VX2 tumor of rabbit was heated by an array of Fe-Pt thermoseeds. Rabbit tibia1 bone with bone tumor was heated by a intramedullary implanted pin made of a ferromagnetic glass-ceramic. Results:The obtained magnetic field strength perpendicular to the axis of the troidal core was uniform inside the core gap. The field sharply attenuated outside the core edge. The maximum field strength at the gap center when gap width was 25 and 10 cm, and at the gap end was 100, 200 and 300-Oe, respectively. Fe-Pt thermoseeds inserted perpendicularly to the skin heated the tumor fairly homogeneously without the automatic reguration. An intramedullar ceramic pin heated the whole bone to 42 ‘C. strong and confined field is Generating an uniform. needed to achieve the temperature homogeneity and’sufficient temperature rise, and to avoid direct tissue In every respect, this heating system is heating. supposed to be superior to the other induction heating system. Conclusion:The new induction heating system generated an uniform and strong magnetic field confined inside the core gap, and effectively heated experimental soft tissue and bone tumors.
11 ANALYSIS OF TEMPERATURE DISTRIBUTIONS OF INTERSTITIAL HYPERTHERMIA USING A HOT WATER SYSTEM. G. Stuecklschweiger, Ph.D.*, K. Arian-Schad, M.D.*, D.S. Kapp, Ph.D., M.D.+, L. Handl-Zeller, M.D.*, and A. Hackl, M.D.* *University Clinic of Radiology, Department of Radiation Therapy, Graz, Austria +Department of Radiation Oncology, Stanford University, Stanford, California, 94305
Purpose: Interstitial hyperthermia (IHT) is being increasingly employed as an adjunct to brachytherapy in the treatment of implantable tumors. Of the several IHT systems available, perhaps the simplest to use are the circulating hot water systems. In clinical trials employing radiation and hyperthermia, thermal parameters, including mean minimal intratumoral temperature, have correlated with clinical outcome. An analysis was therefore undertaken of the thermal distributions obtained during our initial experience with IHT employing steel needles and the KHS9 hot water IHT system. Materials 81Methods: Twenty patients (12 with anal cancers, 5 with recurrent gynecological tumors, and 3 with metastatic melanomas) received a total of 29 IHT treatments in combination with brachytherapy. The IHT goal was to maintain intratumoral temperatures of 42.5% for 40 minutes. Temperatures were monitored by repetitively manually mapping 3-point thermocouple probes at 0.5 cm intervals within one or more hollow needles placed transtumorally for thermometry purposes. The temperature of the water inside the controlled temperature waterbath (Tw), the inflow water temperature (Tin), the outflow watertemperature (Tout), and the intratumoral temperatures were recorded at intervals of 5 seconds. The time to obtain steady-state temperatures and the thermal washout rates were also determined. The intratumoral thermal distributions were characterize-he mean minimum temperature (m), the mean average temperature (G) and the mean maximum temperature (Tmax) for all IHT treatments and for all IHT treatments for each of the three different tumor types. Results: To achieve the desired intratumoral temperatures, maximum, average, and minimum Tw were 49.7%, 48.4%, and 46.2%, respectively. Steady-state intratumoral temperatures were reached in an average time of 4 minutes with a maximum time to steady-state of 6 minutes. For all treatments, the average difference of Tin and Tout was 0.2%. Tmin, Eand Tmax of all treatments were 40.8X, 42.8”C, and 45°C respectively. For the anal carcinomas, the values for these parameters were: 40.8%, 42.4X, 45.0%; for gynecological cancers: 41.0%, 43.2%, 43.9%; and for metastatic melanomas: 42.1%, 42.7’%, and 43.1 “C. Conclusion: The intratumoral thermal distributions obtained with this hot water system appear to be at least as good as those reported for other RF or microwave interstitial systems. This system is relatively inexpensive, simple to use, safe and requires no special treatment room.