1975, British Journal of Radiology, 48, 390-391
Comparison of skin erythemas under two different fractionation schemes By P. Angelakis, M.D., D.M.R.T., F.R.C.R., N. Throuvalas, M.D., G. Paraskevas, M.D., D M RT and G. Pontifix, M.D. Department of Radiology, School of Medicine, Athens University, Aretaieon Hospital, Vas. Sophias Aue. Athens, Greece {Received September, 1973) ABSTRACT
weekly should be tried in order to find its equivalent to 200 rads five times per week. This was the basis for a new clinical trial.
This paper reports the results of a prospective clinical trial comparing 200 rads daily five times weekly for four weeks with 400 rads twice weekly for four weeks. Total dose in the first case was 4,000 rads and in the second 3,200 rads. Thirty patients treated palliatively for bronchial carcinoma are involved in this report. Treatment was given at 220 kV and the intensity of skin erythema at the end of the treatment was the measure of comparison. Generally 200 rads daily five times weekly for four weeks produced more intense erythema than the other scheme used.
In radiotherapy it is common practice to use daily fractionation schemes, treating patients five or six days weekly for five to seven weeks. In this way, the doses given are about 200 rads daily up to a total dose of 6,000 rads. Radiotherapists wishing to use different fractionation regimes have little data to guide them in the choice of the number of fractions, dose per fraction, and total dose. Ellis (1969) has put forward the concept of Nominal Standard Dose as a first attempt to systemize a relationship between the dose, time, number and size of fractions, and has recently published detailed tables based on it (Ellis, 1973). Fowler (1965) produced two curves relating total dose, number of fractions, and dose per fraction based on clinical and experimental information. Shuttleworth and Fowler (1966) prepared a nomogram relating total dose, dose per fraction, and number of fractions to both the equivalent single dose and equivalent total dose in 30 fractions for normal tissue reaction. At this centre we recently published the results of a clinical trial based on the nomogram of Shuttleworth and Fowler (Angelakis, Papavasiliou and Elias, 1973). We compared 200 rads skin dose daily, five times per week, with its equivalent dose (according to the nomogram 380 rads skin dose twice weekly), on normal skin by observing the degree of skin erythema and on malignant tumours by observing the degree of tumour destruction. Both regimes were used on the same patient. It was concluded that in general, 200 rads five times per week had a superior biological effect in comparison to 380 rads given twice weekly. Fowler, discussing these results, suggested that a higher dose to 380 rads twice
MATERIAL AND METHODS
In the radiotherapy department of the Medical School of the University of Athens, we treat patients with advanced bronchial carcinoma on a palliative basis. A straight-on anterior or posterior field is applied to the tumour-bearing area, that is, the primary and the mediastinum. Field size is 20 X 10 cm. Half of it, i.e. 10x10 cm, is treated five days per week, Monday to Friday, or Tuesday to Saturday, and the other half twice weekly, i.e., Monday and Thursday, or Tuesday and Friday. Patients are
FIG. 1. To show difference of skin erythema in two, side by side. 10x10 cm fields.
390
MAY
1975
Comparison of skin erytnemas under two different fractionation schemes treated with conventional X rays at 220 kV, 15 mA, Fil. 1 mm cu, 1 mm Al, at 50 cm FSD. The area treated five times weekly receives a skin dose of 200 rads daily and the other one a skin dose of 400 rads twice weekly. Total dose for the first fractionation regime is 4,000 rads and for the second one 3,200 rads. Treatment time for most cases was 26 days except for cases where the treatment time was extended because of holidays or short breaks. Every patient was examined every Tuesday during treatment and at the end of it or a few days afterwards, by three or more members of the staff, all of whom except one did not know which area was treated with the two different fractionation regimes. The intensity of the skin erythema was recorded each time and in many patients a photograph was taken (Fig. 1). RESULTS
Thirty patients entered the clinical trial, but only 25 completed treatment (Table I). Of these, 19 at the end of their treatment showed a brisker erythema in the field that was treated with 200 rads five days weekly to a total dose of 4,000 rads. Four TABLE I TOTAL TREATMENT TIME I \ DAYS FOR THE 25 PATIENTS CONGESTIVE TREATMENT AND THE INTENSITY OF THE SKIN ERYTHEMA FOR EACH FRACTIONATION REGIME
Total treatment time iti days
Intensity of skin erythema Greater with
Initials l.EK 2. IK 3.PN 4. NN 5. TM 6.GM 7. GM 8.PM 9. NL 10. NL 11.IB 12. GK 13. PK 15. SK 16. DK 19. PT 20. AS 21. GL 24. GD 25. KG 26. DF 27. KF 28. AP 29. DZ 30. EK
200
400
rads
rads
200
25 26 26 28 27 26 25 26 25 27 25 26 26 26 26 29 26 25 27 25 26 25 26 25 29
_j_
26 28 28 34 29 28 26 28 26 30 26 28 28 28 28 30 28 26 28 26 28 26 27 26 31
.
400
Equal
j -
-1-
patients showed a brisker erythema in the field that received 400 rads twice weekly to a total of 3,200 rads, while in two others, both areas developed erythema of the same intensity. The difference is statistically significant. The result is even more significant as, in general, treatment times were slightly shorter in the 400 rads twice weekly cases and consequently the intensity of skin erythema was recorded in a relatively shorter time after the completion of the 200 rads five times per week cases. It would have been desirable for treatment with the two different fractionation regimes to start and finish at the same day, but this is not possible with these fractionation techniques. DISCUSSION
Up to now, data used by different authors to establish a relationship between time, size, and number of fractions, as well as total dose, were based either on cellular experiments or on a retrospective study of clinical cases. Angelakis et al. (1973) published a prospective clinical trial and found that the two proposed doses were not equivalent. Recently, and after the completion of this clinical trial, Ellis (1973) published tables which can be used to change from one fractionation system to another. Two hundred rads daily five times weekly to a total of 4,000 rads according to these tables is equivalent to a twice-weekly fractionation scheme of 400 rads to a total of 3,200 rads. The results of our prospective clinical trial show that 400 rads twice weekly to a total dose of 3,200 rads is biologically inferior to 200 rads daily, five times weekly to a total dose of 4,000 rads as regards their ability to produce the same intensity of skin erythema at the completion of treatment. Liversage (1971), when changing from daily to less fractionation, suggests a somewhat smaller reduction in the total dose and we feel that he is correct.
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r
i"
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REFERENCES ANGELAKIS, P., PAPAVASILIOU, C ,
J-
and
ELIAS, C ,
1973.
Twice per week treatment versus five times per week. A radiotherapeutic clinical trial. British Journal of Radiology, 46, 350-353. ELLIS, F., 1969. Dose, time and fractionation: a clinical hypothesis. Clinical Radiology, 20, 1—8. 1973. A simplification in the use of the NSD concept in practical radiotherapy. British Journal of Radiology, 46, 529-537. FOWLER, J. F., 1971. Personal communication. 1965. The estimation of total dose for different numbers of fraction in radiotherapy. British Journal of Radiology, 38, 365-368. LIVERSAGE, W. E., 1971. A critical look at the ret. British Journal of Radiology, 44, 91-100. SHUTTLEWORTH, E., and FOWLER, J. F., 1966. Nomograms
for radiobiologically equivalent fractionated doses. British Journal of Radiology, 39, 154. 391
X-ray
Comparison of skin erythemas under two different fractionation schemes By P. Angelakis, M.D., D.M.R.T., F.R.C.R., N. Throuvalas, M.D., G. Paraskevas, M.D., D M RT and G. Pontifix, M.D. Department of Radiology, School of Medicine, Athens University, Aretaieon Hospital, Vas. Sophias Aue. Athens, Greece {Received September, 1973) ABSTRACT
weekly should be tried in order to find its equivalent to 200 rads five times per week. This was the basis for a new clinical trial.
This paper reports the results of a prospective clinical trial comparing 200 rads daily five times weekly for four weeks with 400 rads twice weekly for four weeks. Total dose in the first case was 4,000 rads and in the second 3,200 rads. Thirty patients treated palliatively for bronchial carcinoma are involved in this report. Treatment was given at 220 kV and the intensity of skin erythema at the end of the treatment was the measure of comparison. Generally 200 rads daily five times weekly for four weeks produced more intense erythema than the other scheme used.
In radiotherapy it is common practice to use daily fractionation schemes, treating patients five or six days weekly for five to seven weeks. In this way, the doses given are about 200 rads daily up to a total dose of 6,000 rads. Radiotherapists wishing to use different fractionation regimes have little data to guide them in the choice of the number of fractions, dose per fraction, and total dose. Ellis (1969) has put forward the concept of Nominal Standard Dose as a first attempt to systemize a relationship between the dose, time, number and size of fractions, and has recently published detailed tables based on it (Ellis, 1973). Fowler (1965) produced two curves relating total dose, number of fractions, and dose per fraction based on clinical and experimental information. Shuttleworth and Fowler (1966) prepared a nomogram relating total dose, dose per fraction, and number of fractions to both the equivalent single dose and equivalent total dose in 30 fractions for normal tissue reaction. At this centre we recently published the results of a clinical trial based on the nomogram of Shuttleworth and Fowler (Angelakis, Papavasiliou and Elias, 1973). We compared 200 rads skin dose daily, five times per week, with its equivalent dose (according to the nomogram 380 rads skin dose twice weekly), on normal skin by observing the degree of skin erythema and on malignant tumours by observing the degree of tumour destruction. Both regimes were used on the same patient. It was concluded that in general, 200 rads five times per week had a superior biological effect in comparison to 380 rads given twice weekly. Fowler, discussing these results, suggested that a higher dose to 380 rads twice
MATERIAL AND METHODS
In the radiotherapy department of the Medical School of the University of Athens, we treat patients with advanced bronchial carcinoma on a palliative basis. A straight-on anterior or posterior field is applied to the tumour-bearing area, that is, the primary and the mediastinum. Field size is 20 X 10 cm. Half of it, i.e. 10x10 cm, is treated five days per week, Monday to Friday, or Tuesday to Saturday, and the other half twice weekly, i.e., Monday and Thursday, or Tuesday and Friday. Patients are
FIG. 1. To show difference of skin erythema in two, side by side. 10x10 cm fields.
390
MAY
1975
Comparison of skin erytnemas under two different fractionation schemes treated with conventional X rays at 220 kV, 15 mA, Fil. 1 mm cu, 1 mm Al, at 50 cm FSD. The area treated five times weekly receives a skin dose of 200 rads daily and the other one a skin dose of 400 rads twice weekly. Total dose for the first fractionation regime is 4,000 rads and for the second one 3,200 rads. Treatment time for most cases was 26 days except for cases where the treatment time was extended because of holidays or short breaks. Every patient was examined every Tuesday during treatment and at the end of it or a few days afterwards, by three or more members of the staff, all of whom except one did not know which area was treated with the two different fractionation regimes. The intensity of the skin erythema was recorded each time and in many patients a photograph was taken (Fig. 1). RESULTS
Thirty patients entered the clinical trial, but only 25 completed treatment (Table I). Of these, 19 at the end of their treatment showed a brisker erythema in the field that was treated with 200 rads five days weekly to a total dose of 4,000 rads. Four TABLE I TOTAL TREATMENT TIME I \ DAYS FOR THE 25 PATIENTS CONGESTIVE TREATMENT AND THE INTENSITY OF THE SKIN ERYTHEMA FOR EACH FRACTIONATION REGIME
Total treatment time iti days
Intensity of skin erythema Greater with
Initials l.EK 2. IK 3.PN 4. NN 5. TM 6.GM 7. GM 8.PM 9. NL 10. NL 11.IB 12. GK 13. PK 15. SK 16. DK 19. PT 20. AS 21. GL 24. GD 25. KG 26. DF 27. KF 28. AP 29. DZ 30. EK
200
400
rads
rads
200
25 26 26 28 27 26 25 26 25 27 25 26 26 26 26 29 26 25 27 25 26 25 26 25 29
_j_
26 28 28 34 29 28 26 28 26 30 26 28 28 28 28 30 28 26 28 26 28 26 27 26 31
.
400
Equal
j -
-1-
patients showed a brisker erythema in the field that received 400 rads twice weekly to a total of 3,200 rads, while in two others, both areas developed erythema of the same intensity. The difference is statistically significant. The result is even more significant as, in general, treatment times were slightly shorter in the 400 rads twice weekly cases and consequently the intensity of skin erythema was recorded in a relatively shorter time after the completion of the 200 rads five times per week cases. It would have been desirable for treatment with the two different fractionation regimes to start and finish at the same day, but this is not possible with these fractionation techniques. DISCUSSION
Up to now, data used by different authors to establish a relationship between time, size, and number of fractions, as well as total dose, were based either on cellular experiments or on a retrospective study of clinical cases. Angelakis et al. (1973) published a prospective clinical trial and found that the two proposed doses were not equivalent. Recently, and after the completion of this clinical trial, Ellis (1973) published tables which can be used to change from one fractionation system to another. Two hundred rads daily five times weekly to a total of 4,000 rads according to these tables is equivalent to a twice-weekly fractionation scheme of 400 rads to a total of 3,200 rads. The results of our prospective clinical trial show that 400 rads twice weekly to a total dose of 3,200 rads is biologically inferior to 200 rads daily, five times weekly to a total dose of 4,000 rads as regards their ability to produce the same intensity of skin erythema at the completion of treatment. Liversage (1971), when changing from daily to less fractionation, suggests a somewhat smaller reduction in the total dose and we feel that he is correct.
-j-
_t_L -j-i-
-h -
r
i"
• 1 -
-j~r -L
-1-\—
REFERENCES ANGELAKIS, P., PAPAVASILIOU, C ,
J-
and
ELIAS, C ,
1973.
Twice per week treatment versus five times per week. A radiotherapeutic clinical trial. British Journal of Radiology, 46, 350-353. ELLIS, F., 1969. Dose, time and fractionation: a clinical hypothesis. Clinical Radiology, 20, 1—8. 1973. A simplification in the use of the NSD concept in practical radiotherapy. British Journal of Radiology, 46, 529-537. FOWLER, J. F., 1971. Personal communication. 1965. The estimation of total dose for different numbers of fraction in radiotherapy. British Journal of Radiology, 38, 365-368. LIVERSAGE, W. E., 1971. A critical look at the ret. British Journal of Radiology, 44, 91-100. SHUTTLEWORTH, E., and FOWLER, J. F., 1966. Nomograms
for radiobiologically equivalent fractionated doses. British Journal of Radiology, 39, 154. 391
X-ray
