RADIUM TREATMENT FOR HEMANGIOMA IN EARLY CHILDHOOD

Acia Oncologica 29 (1990) Fax. 5 FROM THE DEPARTMENT OF HOSPITAL PHYSICS, AND THE DEPARTMENTS OF GENERAL ONCOLOGY AND CANCER PREVENTION, RADIUMHEMMET, KAROLINSKA HOSPITAL, STOCKHOLM, SWEDEN. RADIUM TREATMENT FOR HEMANGIOMA IN EARLY CHILDHOOD Reconstruction and dosimetry of treatments, 1920-1 959 Abstract Between 1920 and 1959, a total of 14647 children younger than 18 months were treated at Radiumhemmet with ionizing radiation for skin hemangioma. Seventy-two percent of the children were treated with radium needles or tubes, which were put into glass capsules and then applied to the hemangioma. The absorbed doses to different organs have been measured in a tissue equivalent phantom, representing a 6-month-old child. For a standard treatment of 8 Gy to the hemangioma the mean absorbed doses to the brain, eye lens, parotid gland, thyroid, breast anlage and gonads from 28 different treatment areas were 0.03-0.2 Gy. The mean absorbed dose to the organs in younger (<2 months) and older (14-18 months) children were up to 50% higher (0.04-0.1 Gy) and 33% lower (0.02-0.06 Gy) respectively, than for a 6-month-old child. The uncertainty in organ absorbed doses for each patient depended mostly on the estimation of the distance between the applicator and the site. Key words: Hemangioma, radium dosimetry, children, ionizing radiation. The carcinogenic effect of ionizing radiation has mainly been studied in populations of exposed adults ( 14. Studies of exposed children have in general been based on small populations and the absorbed doses have often been uncertain (2-8). Several of these studies have reported a higher sensitivity to radiation carcinogenesis than after exposure in adult life. In order to relate the cancer risk to the absorbed dose in children, the doses to the head, neck and breast regions have been measured in phantoms during x-ray treatment for tinea capitis and thymus enlargement (7, 9, 10). Organ doses have also been calculated for children exposed to the nuclear bombs in Hiroshima and Nagasaki or after treatment for pediatric malignancies (3, 4, 8, 11). Hemangiomas are common benign skin lesions of early childhood. Although they usually undergo spontaneous M. LUNDELL, C. J. FURST, B. HEDLUND and L.-E. HOLM regression, radiotherapy was previously frequently used to facilitate the regression and healing of the lesions. Radiotherapy for skin hemangioma was introduced at Radiumhemmet in 1909 and was used until the 1950s (12, 13). During the period 1909-1959, approximately 16000 patients with skin hemangioma received radiotherapy at Radiumhemmet. The mortality and the cancer incidence have previously been studied in those patients irradiated at Radiumhemmet between 1920 and 1959 (14, IS). Significantly increased risks were found for breast cancer and soft tissue tumors and for all sites combined. The cancer mortality was significantly increased only for all cancer sites combined (15). In a case-control study based on the material from Radiumhemmet a dose-response relationship was found for thyroid cancer as well as for tumors of bone and soft tissues. For breast cancer no such relationship could be detected (16). The purpose of the present study was to reconstruct the treatments of skin hemangioma with radium needles and tubes in a 6-month-old child and to perform dosimetry calculations for these treatment techniques. Material and Methods Dosimetry and dose calculations were performed for treatments given during the period 1920-1959 and for children less than 18 months of age at the first treatment. Information about irradiation given before 1920 was insufficient and, as regards the older children, the estimation of absorbed dose would be more uncertain and inaccurate, Accepted for publication 28 April 1989. 551

~ ~ 552 M. LUNDELL ET AL. Fig. 1. Applicators in two rows with extra ones along the sides. Fig. 2. Phantom divided into 28 areas. Table 1 Table 2 Number of treated patients 1920-1959, 0-18 months of age Period Radium-226 x-rays Phospho- Total rous-32 1920-1929 399 0 0 399 1930-1939 1529 2 0 I531 1940-1949 7061 462 0 7 523 1950-1959 3219 1944 31 5 194 Total 12 208 2 408 31 14 647 especially so when information about height and weight was missing. The lesions were treated with radium-226, x-rays or phosphorus-32. The treatment techniques varied during the different decades (Table 1) and with the size and type of hemangioma. Radium treatments were most commonly performed by flat applicators, needles or tubes placed on the lesion. In some cases tele-radium treatment was used. The most common radium treatment modalities were needles and tubes in glass cases applied to the skin. The needles and tubes had a mean activity of 370 and 300 MBq respectively. The glass cases ensured a specified distance of 4.5 mm to the skin, 4.5 mm between the needles and 5.0 mm between the tubes. The applicators were arranged to cover the hemangioma with some margin and were usually put in one or two rows. Applicators along the sides were sometimes used (Fig. 1). The desired absorbed dose was defined as the average dose to the first 10 mm of tissue, usually 6-9 Gy (12). Four needles or 10 tubes were mostly used for one treatment (range 2-88 and 1-41 respectively) and the treatment time was then 2 h 37 min. The treatment times were tabulated for different numbers of applicators to achieve an average dose of 8 Gy. In general no shielding Correction of distances (%) in relation to size at 6 months of age -~ ~ Age (months) Treated body region <2 2-4.9 5-8.9 9-13.9 14-17.9 1. Within trunk/ -20-10 0 +10 +15 extremities 2. Within headheck -15-5 0 +7 +10 3. Between regions -15-5 0 +7 +10 1 and 2 of adjacent tissues was used and the child mostly sat in the mother s lap or lay on a couch during the treatment. Dosimetry studies were performed on a phantom of the same type as that designed by Lundberg (17) in Gothenburg, Sweden, in a study of children irradiated for skin hemangiomas. Our phantom was molded to resemble a 6-month-old child, i.e. the mean age at the first treatment, in a supine position with the head and extremities somewhat bent. The dimensions were extracted from a study of growth development of Swedish children (18). In that study data were collected by repeated measurements on 212 children born between 1955 and 1958. The supine length of our phantom, with knees bent, was 60 cm and the crown-rump length was 43 cm. Dosimetry calculations were made for 5 different age-groups: <2 months, 2-4.9 months, 5-8.9 months (corresponding to the phantom), 9-13.9 months, and 14-17.9 months. The correction of body size for different ages was based on the same study (Table 2). The size of the lungs and the location of the gonads in the phantom were determined by a pediatric radiologist. The phantom was made of a tissue equivalent material (Wacher m-polymer 444 Z) with a density of 1.03 x lo3 kg/m3. Cork (density 3 x lo2 kg/m3) was the substitute for lung tissue.

DOSIMETRY OF RADIUM TREATMENT FOR HEMANGIOMA 553 testicles was estimated as the mean value from the dosimeters in these organ sites and for the eye lenses, parotid glands, and breast anlage as the mean value from the right and left dosimeters. The absorbed dose in various organs (brain. eye lenses, parotid glands, thyroid, breast anlage and gonads) was estimated by taking the mean value of the measured dose, to the organ, from the 28 different treatment locations. As the differences between the doses to the ovaries and the testicles were minor, they were combined as gonad doses. Corrections for two age groups, <2 months and 14-17.9 months were made considering the differences in body size according to Karlberg et al. (18). Only the youngest and the oldest age groups were chosen since the differences between adjacent groups were rather small. Fig. 3. Phantom and cross sections with dosimeter locations. Table 3 Mean absorbed dose (rngy), for an irradiation of 1 GBqh, in various organs from different body regions Mean absorbed dose (rngy) Treated Brain Eye Parotid Thyroid Breast Gonads body region lens gland anlage Headlneck 17 22 22 26 18 2 Upper trunk 4 9 12 24 53 6 Lower trunk 1 3 3 4 14 31 Extremities 1 2 2 3 4 15 The location of the hemangiomas was coded according to a division of the phantom into 28 areas (Fig. 2). This was possible since hospital records, photographs and treatment records with drawings of the treatment sites and the position of the applicators were available for nearly all patients. In the dose calculations it was assumed that all treatments be given at the center of each area. Each compartment of the phantom was irradiated separately, most often with one row of 5 radium tubes placed in the center. The 10 original tubes and original glass cases still available at Radiumhemmet were used in the study. To measure the absorbed dose to various organs, thermoluminescence dosimeters (TLD) were used. They were made of lithiurnfluoride, 0.9 mm thick and with a diameter of 4.5 mm. The head of the phantom was divided into 2 sections and dosimeters were applied in 9 equally distributed spots of the location of the brain and 1 in each of the locations of the thyroid lobes. Three dosimeters were placed anteroposteriorly at the place of each ovary. Small cavities were drilled for the dosimeters at the site of the eye lenses, parotid glands, and breast anlage. The testicle dose was measured on the phantom surface (Fig. 3). The absorbed dose in the brain, thyroid, ovaries, and Results The mean values of the measurements of absorbed doses, for an irradiation of 1 GBqh from the body regions to the various organs are presented in Table 3. The absorbed dose decreased with a factor 20 when the treatment location and the organ were not in the same body region. In order to achieve an estimate of the absorbed dose in various organs, the doses to the brain (7 mgy), eye lens (10 mgy), parotid gland (11 mgy), thyroid (16 mgy), breast anlage (20 mgy) and gonads (1 1 mgy) in a 6-month-old child were calculated as the mean dose from the 28 different treatment locations when irradiated with 1 GBqh (Table 4). A treatment with the average dose of 8 Gy as recommended by Strandqvist (12) required an application of 4 radium needles or 10 tubes during 2 h 37 min. Such a treatment using needles would give an absorbed dose to the brain of 0.03 Gy as a mean from all treatment areas. The mean absorbed dose in the eye lens would be 0.04 Gy, in the parotid gland 0.04 Gy, in the thyroid 0.06 Gy, in the breast anlage 0.08 Gy, and in the gonads 0.04 Gy. The less common treatments with tubes yielded twice as high absorbed doses to the organ (Table 5). Discussion The absorbed doses corresponding to a standardized treatment of 8 Gy to the hemangioma in the irradiated cohort were lower than in the populations of children irradiated for tinea capitis and thymus enlargement (7, 9, 10, 19-21; Table 6). In the study of children irradiated for hemangiomas in Gothenburg (S. Lindberg, personal communication) the calculated absorbed doses after a standardized treatment were twice as high as in our study, but still lower than the doses in the comparative studies. In a case-control study from Radiumhemmet of patients irradiated for skin hemangioma, dosimetry was made for selected tumor sites including the brain, thyroid and breasts (16). The mean absorbed doses for the cases

554 M. LUNDELL ET AL Table 4 Mean absorbed dose (mgy) and range, for an irradiation of 1 GBqh, in the brain, eye lens, parotid gland, thyroid, breast anlage and gonads in relation to age (months) at treatment Brain Eye lens Parotid gland Thyroid Breast anlage Gonads Age Mean Range Mean Range Mean Range Mean Range Mean Range Mean Range <2 10 1-46 14 2-58 15 2-38 24 2-98 34 3-246 11 1-47 5-8.9 7 1-35 10 148 I1 1-3 1 16 1-63 20 2-130 8 1-32 14-17.9 6 1-28 8 140 9 1-27 12 144 16 1-109 6 1-26 Table 5 Mean organ absorbed doses (Gy) to the brain, eye lens, parotid gland, thyroid, breast anlage and gonads from a standard treatment with 4 needles or 10 tubes of radium-226 Brain Eye lens Parotid gland Thyroid Breast anlage Gonads Treated body region Needles Tubes Needles Tubes Needles Tubes Needles Tubes Needles Tubes Needles Tubes Headlneck 0.07 0.13 0.08 0.17 0.09 0.17 0.10 0.20 0.07 0.14 <0.01 0.02 Upper trunk 0.01 0.03 0.04 0.07 0.04 0.09 0.09 0.19 0.20 0.41 0.02 0.05 Lower trunk ~0.01 <0.01 0.01 0.03 0.01 0.02 0.02 0.03 0.05 0.11 0.12 0.24 Extremities <0.01 ~0.01 <0.01 0.02 co.01 0.02 0.01 0.02 0.01 0.03 0.06 0.12 Mean value 0.03 0.06 0.04 0.08 0.04 0.09 0.06 0.12 0.08 0.16 0.04 0.09 Table 6 Absorbed doses (Gy) and dose ranges to the brain, thyroid, and breast anlage in different study populations Study Present study Hemangioma treatment, case-control study (IS) Tinea capitis treatment, US (9, 19) Tinea capitis treatment, Israel (10, 20) Enlarged thymus treatment (7, 21) Hemangioma treatment (S. Lindberg, personal communication) ~ Brain Thyroid Breast anlage Dose Range Dose Range Dose Range Mean 0.03 O.Ol-O.1 0.06 0.01-0.2 0.08 0.01-0.5 Mean 0.1 0.01-1 0.5 0.014 0.2 0.01-8 Median 0.03-0.06-0.03 - Mean 1.4 0.75-1.75 0.06 0.04-0.08 - - Mean 1.3 0.95-1.39 0.09 0.04-0.11 - - - Mean - 1.2 0.05-11 0.69 0.01-7.05 Mean 0.09-0.13-0.17 - and controls were 0.1 Gy, 0.5 Gy, and 0.2 Gy respectively. The median doses, however, were 0.03, 0.06, and 0.03 respectively for the 3 tumor sites which corresponds well with the mean doses in this study. Most patients (6470%) received an absorbed dose of <O. 1 Gy and the reason for the large discrepancy between the mean absorbed dose and the median dose was that a few patients had received high doses which thus increased the mean dose. The phantom used in our study was based on data of children born in the 1950s (18). The children in our study were born during the period 1920-1959 and the phantom might therefore not represent the mean dimensions of a 6-month-old child born during that time. However, Engstrom & Falconer (22) compared the length and weight of Swedish children born 1911-1920 and 1956-1957 respectively. The difference in weight was 0. 15 kg and in length 0.5 cm. These differences cannot affect the results obtained in the present study.

DOSIMETRY OF RADIUM TREATMENT FOR HEMANGIOMA 555 Fig. 4. Drawing and photograph of applicators adjacent to radiosensitive organ. There are several limitations that apply to the estimation of organ doses for individual patients on the basis of the dose rates reported in our study: 1. The measurements were made on a phantom representing a 6-month-old child. The dose to various organs will differ, up to +50%, for children of other sizes. 2. The exact distance between the applicator and the organ sites was uncertain and also the proportions of different kinds of tissues the gamma rays were penetrating. 3. The dose distribution around a radium needle or tube in a glass case is well-known since one needle, 10 tubes and glass cases of the original ones are still available at Radiumhemmet. The position of the needles and tubes is uncertain for each individual. For instance, when the needledtubes are turned 90" the dose rate to an adjacent organ may differ up to about 30% (Fig. 4). In other retrospective studies of cancer risks following radiotherapy exact information about the radiotherapy and the body size of the patients has often been missing. In the present study hospital records, photographs and treatment records with drawings of the treatment sites and the position of the applicators were available for nearly all patients irradiated for skin hemangioma. This will enable individual dosimetry. The incidence of and mortality from cancer in the cohort can then be related to the absorbed dose. ACKNOWLEDGEMENTS This study was supported by the National Institute of Radiation Protection, Stockholm (project No. P208-84/85/88), and the Swedish Cancer Society (project No. 2314-Bg8-02PB). We thank Elisabeth Bjurstedt for excellent assistance in various aspects of this study. Requesrfor reprints: M. Lundell M. Sc., Department of Hospital Physics, Karolinska Hospital, S-10401 Stockholm, Sweden. REFERENCES 1. Committee on the Biological Effects of Ionizing Radiations. The effects on populations of exposure to low levels of ionizing radiation: 1980. Washington, DC: National Academy Press, 1980. 2. United Nations Scientific Committee on the Effects of Atomic Radiation. 1988 Report to the General Assembly, with annexes. Ionizing radiation: sources and biological effects. New York: United Nations, 1988. 3. Finch SC. Leukemia and lymphoma in atomic bomb survivors. In: Boice JD Jr, Fraumeni JR Jr, eds. Radiation carcinogenesis. Epidemiology and biological significance. Progress in cancer research and therapy, vol. 26. New York: Raven Press, 1984: 3744. 4. Tokunaga M, Land CE. Yamamoto T, et al. Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1980. Radiat Res 1987; 112: 243-72. 5. Hempelmann LH. Hall WJ, Phillips M, Cooper RA, Ames WR. Neoplasms in persons treated with x-rays in infancy: fourth survey in 20 years. JNCI 1975; 55: 519-30. 6. Ron E, Modan B. Benign and malignant thyroid neoplasms after childhood irradiation for tinea capitis. JNCI 1980; 65: 7-1 1. 7. Hildreth NG, Shore RE, Hempelmann LH, Rosenstein M. Risk of extrathyroid tumors following radiation treatment in infancy for thymic enlargement. Radiat Res 1985; 102: 378-91. 8. Tucker MA, D'Angio GJ. Boice JD Jr. et al. Bone sarcomas linked to radiotherapy and chemotherapy in children. N Engl J Med 1987; 317: 588-93. 9. Schultz RJ, Albert RE. 111. Dose to organs of the head from the X-ray treatment of tinea capitis. Arch Environ Health 1968; 17: 935-50. 10. Werner A, Modan B, Davidoff D. Doses to brain, skull and thyroid, following X-ray therapy for tinea capitis. Phys Med Biol 1968; 13: 247-58. 11. Sandler DP, Comstock GW, Matanoski GM. Neoplasms following childhood radium irradiation of the nasopharynx. JNCI 1982; 68: 3-8. 12. Strandqvist M. Radium treatment of cutaneous cavernous haemangiomas, using surface application of radium tubes in glass capsules. Acta Radio1 1939; 20: 185-211. 13. Fiirst CJ, Lundell M, Holm L-E. Radiation therapy of hemangiomas, 1909-1959. A cohort based on 50 years of clinical practice at Radiumhemmet, Stockholm. Acta Oncol 1987: 26: 33-6. 14. Fiirst CJ, Lundell M, Holm L-E, Silfversward C. Cancer incidence after radiotherapy for skin hemangioma-a Swedish retrospective cohort study. JNCI 1988; 80: 1387-92. 15. Fiirst CJ, Silfversward C, Holm L-E. Mortality in a cohort of radiation treated childhood skin hemangiomas. Acta Oncol 1989; 28: 789-94. 16. Fiirst CJ, Lundell M, Holm L-E. Tumors after radiotherapy for skin hemangioma in childhood. A case-control study. Acta Oncol 1990 (Accepted for publication). 17. Lundberg LM. StrPldoser till spadbarn som fptt radiumbehandling for medfodda hemangiom. Rapport RADFYS 83: 04. Goteborg: Radiofysiska institutionen, Sahlgrenska sjukhuset, 1983. (In Swedish.) 18. Karlberg P, Taranger J, Engstrom I. et al. Physical growth from birth to 16 years and longitudinal outcome of the study during the same age period. Acta Paediatr Scand 1976: (Suppl 258): 7-76. 19. Harley NH, Albert RE, Shore RE, Pasternack BS. Follow-up study of patients treated by X-ray epilation for tinea capitis. Estimation of the dose to the thyroid and pituitary glands and other structures of the head and neck. Phys Med Biol 1976; 21: 631-42.

556 M. LUNDELL ET AL 20. Modan B, Ron E, Werner A. Thyroid cancer following scalp irradiation. Radiology 1977; 123: 7414. 21. Shore RE, Woodard E, Hildreth N, Dvoretsky P, Hempelmann L, Pasternack B. Thyroid tumors following thymus irradiation. JNCI 1985; 74: 1177-84. 22. Engstrom L, Falconer B. En jamforelse mellan svenska nyfodda barns langd och vikt 1911-1920 och 1956-1957. Lakartidningen 1960; 57: 1750-5. (In Swedish.)