INT.J. HYPERTHERMIA, 1990, VOL.6, NO.
5, 881-890
Thennoradiotherapy of patients with locally advanced carcinoma of the rectum B. A. BERDOV and G. Z. MENTESHASHVILI Research Institute of Medical Radiology, USSR Academy of Medical Sciences, Obninsk, USSR
Int J Hyperthermia Downloaded from informahealthcare.com by University of Queensland on 06/24/13 For personal use only.
(Received 10 July 1989; revised 20 October 1989; accepted 27 November 198% The effectiveness of local hyperthermia was investigated in 56 patients with locally advanced carcinoma of the rectum ( T , N W . All received combined heat and radiation therapy as a pre-operative treatment. The control group consisted of 59 patients with the same stage of disease as those who were only irradiated. Both groups of patients underwent the same surgical procedure. The total tumour dose of ionizing radiation was 40 Gy in 10 fractions, three times a week. The tumour was heated four or five times to a maximum of 42-43 "C by electromagnetic waves with a frequency of 905 MHZ before irradiation. Each heating session lasted 60 min. Patients were selected on the principle of randomization: 16.1% of patients (n=9; n: actual number of patients) showed complete response and 53.6% (n=30) showed significant regression of the primary tumour compared with 1.7% (n= 1) and 33.9%(n=20) in the control group, respectively. The differences were significant @10-0 cm
16.9 78-0 5.1
46 3
Total
59 Table 4. Distribution of patients according to histology of tumour.
Histology
Thennoradiotherapy
Radiation therapy
Adenocarcinoma Signet ring cell carcinoma Squamous cell carcinoma Undifferentiated carcinoma Colloid carcinoma Mucinous carcinoma
51 3 1 1
52 2 1 1 .2 1
Total number of patients
56
59
-
-
2.3. Methods of pre-operative thennoradiotherapy Total tumour dose of ionizing radiation was 40 Gy in 10 fractions, three times a week. The tumour was heated four or five times up to 42-43°C by electromagnetic waves with a frequency of 915 MHz. Local hyperthermia was provided by Soviet heat equipment, the basic parameters of which are given in table 5. An intracavitary antenna supplied with a temperature-controllingdevice delivered heat to tumour tissues at different depths, with avoidance of excessive heating of the adjacent normal tissues. A therapeutic level of temperature (42-43°C) was reached during the first 5-10 min of heating and was maintained for 1 h automatidy. Temperature measurement Table 5 . Basic parameters of electromagnetic heat equipment. ~~~~
2450 f 49 12-6
'Yakhta-3' 915*12.81 33
433-92*0-87 65
*Om5
zt0-5
*0-5
*0-3
*0*3
zk0-3
3-9
2-10
5-30
5
5-10
10-15
4-5 0.7-1.8
7-8 0-8-1-8
Technical characteristics
'Yakhta-2'
Generator frequency (MHz) Wavelength (cm) Automatic temperature control ("C) Error of temperature measurement ("C) Sizes of areas heated by external radiators (cm2) Length of areas heated by intracavitary radiators (cm) Maximal depth of heating (cm) Diameters of intracavitary radiators (cm)
2-3 0.7-1.8
TYakhta' (yacht) - name of the Soviet heating device.
'Yakhta4f
884
B. A. Berdov and G. Z. Menteshashvili
of heat distribution inside the tumour was carried out in seven female patients with carcinoma of the lower part of the rectum when temperature probes were extended into the vagina. Two thermocouples were inserted into the tumour with distances of 0 5 and 1 cm from heating antenna. Temperature in the periphery was measured from the side of the vagina, measuring 42°C. Data on heat distribution inside the tumour in a female patient with carcinoma of the lower part of the rectum are given in figure 1. This pattern of temperature distribution inside the tumour was used as the basis for optimization of temperature regimens in all the following patients. Based on data available in current literature we think that hyperthenka is more effective when it precedes radiation therapy (Field and Blechen 1979, Perez et al. 1981, Dewhirst and Sim 1984, Sapozink et al. 1986). We started hyperthermia from the third radiation session in order to reduce the risk of possible metastases. Radiation was administered 10 min after each heating session.
Int J Hyperthermia Downloaded from informahealthcare.com by University of Queensland on 06/24/13 For personal use only.
-
2.4. Treatment protocol
Treatment protocol for both groups of patients consisted of three consecutive stages. 1. Pre-operative radiation therapy combined with local hyperthermia or alone. 2. Interval of 4 weeks necessary for maximal yield of therapeutic effects and for controuing
side-effects. 3. In case of a sufficient therapeutic effect-radical surgery.
If the level of tumour regression was not sufficient for radical surgery, radiation therapy was continued to a total tumour dose of 80 Gy. 2.5. Evaluation of results of treatment
To evaluate the effectiveness of thennoradiotherapy all the patients were examined before treatment and 3 weeks after it. The examination included palpation of the tumour, ultrasound examination of different lymph nodes and the liver, transrectal ultrasound examination of the primary tumour and pararectal lymph nodes, selective mesentericography , radioimmunological status, and histological examination of the tumour.
Figure 1. Heat distribution inside the tumour in a female patient with carcinoma of the lower part of the rectum.
Locally advanced carcinoma of the rectum
885
Int J Hyperthermia Downloaded from informahealthcare.com by University of Queensland on 06/24/13 For personal use only.
3. Results 3.1. Radiation reactions Nineteen of 56 patients exhibited common radiation reactions, such as general weakness, loss of appetite, vertigo, nausea, etc., following thennoradiotherapy (33 -9% f 6 - 3 %) and 21 of 59 patients following radiation therapy alone (35-6*6-3%). These reactions developed at the dose of 30-35 Gy. They were managed with medication during the 5-7 days after irradiation. Besides common radiation reactions we evaluated local radiation reactions. Frequency and characteristics of local radiation reactions are shown in table 6. Among local radiation reactions, rectitis occurred most frequently. 3.2. Twnour response The evaluation of the effectiveness of treatment was based on local tumour response. Tumour responses were graded as complete, pamal, no response or lack of effect. complete tumour regression or no evidence of disease (NED) was qualified as complete response; partial response signifieda more than 50 % but less than 1005% decrease in tumour volume, no response signified a less than 50% decrease in -our volume, and lack of effect indicated no tumour regression at all. Data on regression of the primary tumour are given in table 7. Tumour response following thermoradiotherapy was more pronounced. The differences were significant (pso96
5, 881-890
Thennoradiotherapy of patients with locally advanced carcinoma of the rectum B. A. BERDOV and G. Z. MENTESHASHVILI Research Institute of Medical Radiology, USSR Academy of Medical Sciences, Obninsk, USSR
Int J Hyperthermia Downloaded from informahealthcare.com by University of Queensland on 06/24/13 For personal use only.
(Received 10 July 1989; revised 20 October 1989; accepted 27 November 198% The effectiveness of local hyperthermia was investigated in 56 patients with locally advanced carcinoma of the rectum ( T , N W . All received combined heat and radiation therapy as a pre-operative treatment. The control group consisted of 59 patients with the same stage of disease as those who were only irradiated. Both groups of patients underwent the same surgical procedure. The total tumour dose of ionizing radiation was 40 Gy in 10 fractions, three times a week. The tumour was heated four or five times to a maximum of 42-43 "C by electromagnetic waves with a frequency of 905 MHZ before irradiation. Each heating session lasted 60 min. Patients were selected on the principle of randomization: 16.1% of patients (n=9; n: actual number of patients) showed complete response and 53.6% (n=30) showed significant regression of the primary tumour compared with 1.7% (n= 1) and 33.9%(n=20) in the control group, respectively. The differences were significant @10-0 cm
16.9 78-0 5.1
46 3
Total
59 Table 4. Distribution of patients according to histology of tumour.
Histology
Thennoradiotherapy
Radiation therapy
Adenocarcinoma Signet ring cell carcinoma Squamous cell carcinoma Undifferentiated carcinoma Colloid carcinoma Mucinous carcinoma
51 3 1 1
52 2 1 1 .2 1
Total number of patients
56
59
-
-
2.3. Methods of pre-operative thennoradiotherapy Total tumour dose of ionizing radiation was 40 Gy in 10 fractions, three times a week. The tumour was heated four or five times up to 42-43°C by electromagnetic waves with a frequency of 915 MHz. Local hyperthermia was provided by Soviet heat equipment, the basic parameters of which are given in table 5. An intracavitary antenna supplied with a temperature-controllingdevice delivered heat to tumour tissues at different depths, with avoidance of excessive heating of the adjacent normal tissues. A therapeutic level of temperature (42-43°C) was reached during the first 5-10 min of heating and was maintained for 1 h automatidy. Temperature measurement Table 5 . Basic parameters of electromagnetic heat equipment. ~~~~
2450 f 49 12-6
'Yakhta-3' 915*12.81 33
433-92*0-87 65
*Om5
zt0-5
*0-5
*0-3
*0*3
zk0-3
3-9
2-10
5-30
5
5-10
10-15
4-5 0.7-1.8
7-8 0-8-1-8
Technical characteristics
'Yakhta-2'
Generator frequency (MHz) Wavelength (cm) Automatic temperature control ("C) Error of temperature measurement ("C) Sizes of areas heated by external radiators (cm2) Length of areas heated by intracavitary radiators (cm) Maximal depth of heating (cm) Diameters of intracavitary radiators (cm)
2-3 0.7-1.8
TYakhta' (yacht) - name of the Soviet heating device.
'Yakhta4f
884
B. A. Berdov and G. Z. Menteshashvili
of heat distribution inside the tumour was carried out in seven female patients with carcinoma of the lower part of the rectum when temperature probes were extended into the vagina. Two thermocouples were inserted into the tumour with distances of 0 5 and 1 cm from heating antenna. Temperature in the periphery was measured from the side of the vagina, measuring 42°C. Data on heat distribution inside the tumour in a female patient with carcinoma of the lower part of the rectum are given in figure 1. This pattern of temperature distribution inside the tumour was used as the basis for optimization of temperature regimens in all the following patients. Based on data available in current literature we think that hyperthenka is more effective when it precedes radiation therapy (Field and Blechen 1979, Perez et al. 1981, Dewhirst and Sim 1984, Sapozink et al. 1986). We started hyperthermia from the third radiation session in order to reduce the risk of possible metastases. Radiation was administered 10 min after each heating session.
Int J Hyperthermia Downloaded from informahealthcare.com by University of Queensland on 06/24/13 For personal use only.
-
2.4. Treatment protocol
Treatment protocol for both groups of patients consisted of three consecutive stages. 1. Pre-operative radiation therapy combined with local hyperthermia or alone. 2. Interval of 4 weeks necessary for maximal yield of therapeutic effects and for controuing
side-effects. 3. In case of a sufficient therapeutic effect-radical surgery.
If the level of tumour regression was not sufficient for radical surgery, radiation therapy was continued to a total tumour dose of 80 Gy. 2.5. Evaluation of results of treatment
To evaluate the effectiveness of thennoradiotherapy all the patients were examined before treatment and 3 weeks after it. The examination included palpation of the tumour, ultrasound examination of different lymph nodes and the liver, transrectal ultrasound examination of the primary tumour and pararectal lymph nodes, selective mesentericography , radioimmunological status, and histological examination of the tumour.
Figure 1. Heat distribution inside the tumour in a female patient with carcinoma of the lower part of the rectum.
Locally advanced carcinoma of the rectum
885
Int J Hyperthermia Downloaded from informahealthcare.com by University of Queensland on 06/24/13 For personal use only.
3. Results 3.1. Radiation reactions Nineteen of 56 patients exhibited common radiation reactions, such as general weakness, loss of appetite, vertigo, nausea, etc., following thennoradiotherapy (33 -9% f 6 - 3 %) and 21 of 59 patients following radiation therapy alone (35-6*6-3%). These reactions developed at the dose of 30-35 Gy. They were managed with medication during the 5-7 days after irradiation. Besides common radiation reactions we evaluated local radiation reactions. Frequency and characteristics of local radiation reactions are shown in table 6. Among local radiation reactions, rectitis occurred most frequently. 3.2. Twnour response The evaluation of the effectiveness of treatment was based on local tumour response. Tumour responses were graded as complete, pamal, no response or lack of effect. complete tumour regression or no evidence of disease (NED) was qualified as complete response; partial response signifieda more than 50 % but less than 1005% decrease in tumour volume, no response signified a less than 50% decrease in -our volume, and lack of effect indicated no tumour regression at all. Data on regression of the primary tumour are given in table 7. Tumour response following thermoradiotherapy was more pronounced. The differences were significant (pso96
