Radiation-induced breast cancer: long-term follow-up of radiation therapy for benign breast disease.

BACKGROUND: From the 1920s through the 1950s, radiation therapy was used in Sweden as a treatment for benign breast diseases. It is now known that exposure of the breast to ionizing radiation increases the relative risk of subsequent breast cancer, especially for younger women. However, the degree to which the patient's age contributes to the elevation of risk for subsequent development of breast cancer is not yet completely understood. PURPOSE: The purpose was to study the risk of breast cancer after irradiation of the female breast and, in particular, to analyze the duration of the effect and the risk for women older than 40 years at first exposure. METHODS: In this cohort study, data were obtained through population-based registers. The exposed group consisted of 1216 women (median age, 40 years) who, during the period spanning 1925 through 1954, received radiation therapy for benign breast disease. The reference group consisted of 1874 women (median age, 36 years) who had the same diagnosis during that time period but did not receive radiation therapy. The radiation doses were determined from the original medical records (mean dose, 5.8 Gy; range, 0.003-50.1 Gy). The follow-up lasted up to 60 years after first exposure. The incidence rate ratio was analyzed with Poisson regression models. RESULTS: The total number of breast cancers in the exposed cohort was 198 versus 101 in the unexposed cohort. Overall, the radiation-associated incidence rate ratio was 3.58 (95% confidence interval = 2.77-4.63). The dose-response gradient was statistically significant (P < .001) but leveled off at higher doses. The incidence rate ratios decreased starting about 25 years after first exposure but were at increased levels throughout the entire follow-up period. The incidence rate ratio decreased with age at first exposure but was significantly increased (P < .001) even when the age at time of first exposure was greater than 40 years. CONCLUSIONS: Total dose, age at first exposure, and time since first exposure were all determinants of the incidence rate ratio of breast cancer after exposure of the breast to ionizing radiation. A statistically significant increase in the incidence of breast cancer following radiation treatment of various benign breast diseases was observed even among women older than 40 years at the time of first treatment. IMPLICATIONS: These findings need to be considered when weighing the relative benefits versus risks of generalized screening of younger women for breast cancer by mammography.

Characteristics of silicon diodes as patient dosemeters in external radiation therapy.

Silicon diodes connected to an integrating instrument that are used to measure the entrance dose on patients undergoing radiation therapy have been investigated with special emphasis on practical clinical aspects. The variation of the diode response for different photon qualities with different field sizes and different irradiation situations including oblique fields, wedges, blocking filters giving different electron contamination have been measured. The diode response for the different situations met in clinical practice when using various electron energies have also been examined. The results from measurements for patients treated with high energy are presented. The study has shown that if the mean value of all measured entrance doses with the diode on a patient differ more than +/- 3% from the presented absorbed dose for 60Co gamma radiation, a correction of the given dose should be made. The corresponding figure for high energy X-rays is +/- 5%.

Quality assurance in conformal radiotherapy: DYNARAD consensus report on practice guidelines.

BACKGROUND AND PURPOSE: Conformal radiotherapy has only recently been widely implemented. Although not all aspects have yet been adequately proven, it is generally recognized that maintaining a high degree of precision throughout the process is critical to the treatment outcome while the focus for quality assurance and quality improvement will need to concentrate more on human factors, procedures, communication, organization and training. A general consensus document on quality assurance guidelines for institutions that deliver conformal radiotherapy treatments to patients has been elaborated within the framework of the DYNARAD/BIOMED concerted action on conformal radiotherapy. The present paper aims to highlight those issues that were identified as of specific importance to conformal radiotherapy. The work reported here further details this guidance by direct correlation with the issues involved in the special case of conformal radiotherapy. METHODS: The DYNARAD document has been drafted in the form of a desktop guide comprising six sets of guidelines and is based on the ESTRO advisory report on 'Quality Assurance in Radiotherapy'. RESULTS AND CONCLUSIONS: The document has been endorsed by the DYNARAD group of institutions. As such it can form the basis for further discussions and enter into the subsequent phase of expanding its consensus basis.

Incidence of primary malignancies other than breast cancer among women treated with radiation therapy for benign breast disease.

This report presents data on the long-term risks of developing malignancies other than breast cancer after exposure to scattered doses of ionizing radiation. The estimates were based on a cohort of 3,090 women who were diagnosed clinically with benign breast disease between 1925 and 1961. A total of 1,216 women were treated with radiation therapy. The breasts received a mean absorbed dose of 5.84 Gy. Mean absorbed doses owing to scatter to 14 other organs were also determined. The lung received the highest mean scattered dose (0.75 Gy; range 0.004-8.98 Gy) and rectum the lowest (0.008 Gy; range 0-0.06 Gy). Median age at first exposure was 40 years. The follow-up lasted up to 61 years after treatment (mean follow-up 27 years). End-point data were obtained from population-based registers. With internal reference the relative risk for non-breast solid tumors was 1.2 (95% confidence interval 1.0-1.5). However, this excess was not apparent when comparison with the general population was made (standardized incidence ratio = 0.95; 95% confidence interval 0.84-1.07). Among individual sites no significantly increased risks were observed. For stomach cancer there was a linear increase with dose (ERR/Gy = 1.3; two-sided P = 0.05). No increased risk was observed for leukemias. In two earlier reports, breast cancer incidence has been shown to be significantly increased in this cohort of irradiated women. Our results suggest that the scattered doses from the breast irradiation may have increased the risk of cancers of other sites, but the small number of cases in different locations precludes strong interpretations.

Postal intercomparison of absorbed dose for high energy x rays with thermoluminescence dosimeters.

This study concerns the accuracy and precision of the IAEA/WHO LiF TLD system used in intercomparison by mail of absorbed doses from 60Co gamma-radiation and 4-25 MV x rays. The system employs 160 mg LiF powder in polystyrene capsules, which are placed at 5 or 7 cm depth in water and irradiated to doses close to 200 rad (2.00 Gy). The dosimeters are mailed to the IAEA Dosimetry Laboratory and read out under conditions to minimize variatons in instrument sensitivity. The precision of the readout technique, using 3 capsules per irradiation and the readout of 5 aliquots per capsule, is characterized by 0.2% standard deviation of the resulting mean. Since random errors during the irradiation are added, the detectable systematic descrepancy in dose delivery, at the 95% confidence level, is +/- 2% for 60Co gamma and +/- 3% for high-energy x rays.

Combined preoperative radiotherapy and surgery in the treatment of carcinoma of the anterior two-thirds of the tongue.

Sixty-three patients with squamous cell carcinoma of the anterior two-thirds of the tongue were treated with preoperative external radiotherapy (mean target dose 42.60 Gray or 4260 rad) and surgery. The expected 5-year survival, expressed as life table estimate of percent of survivors, was 77% for patients with Stage I tumors, 69% with Stage II, and 13% for patients with tumors in Stages III-IV (p less than 0.001). Fourteen patients experienced local recurrences, 7 had homolateral neck metastases, 4 had contralateral neck metastases and 3 had distant metastases. In 15 cases no cancer could be detected at review of the surgical specimens, but 2 of these died of their cancers. In 43 cases cancer was present in the specimens, and 26 of these died of their cancer (p less than 0.01).

Irradiation of rabbit submandibular glands. Histology and morphometry after 15 Gy.

Irradiation of rabbit submandibular glands with a single absorbed dose of 15 Gy caused tissue damage which persisted 4 and 10 months later. The injuries were studied by histology, measurement of gland weights and histomorphometry. Reduction of gland weight due to hypoplasia and missed weight gain were seen and the proportions of the three major intralobular compartments of the glands were altered being dependent on the interval between radiation exposure and observation time. The size of the lobules was reduced and extralobular fibrosis in the hilar region increased. The seromucous acini were partly atrophied, with successively changed architecture and reduced size of the granules. The serous tubules showed pronounced reduction of the granules at 4 months and a remarkable adenomatous regeneration at 10 months post irradiation. The striated ducts were almost unaffected during the observation time. Arteriolar changes were slight to moderate, and there was scarcely any capillary damage. The numbers of intra- and extralobular plasma cells were increased.

Evaluation of the clinical use of TLD.

The relative light output per Gy in water for conventional roentgen radiation (20-190 kV), high energy roentgen radiation (6 and 42 MV) and electrons between 2.2 and 34.5 MeV relative to 60 Co gamma radiation is reported for different kinds of LiF dosemeters. The routine use of LiF dosemeters for a wide range of dosimetry applications in radiation therapy, the handling of the dosemeters to obtain high accuracy and the usefulness of making patient dose measurements are described.

Accuracy of megavolt radiation dosimetry using thermoluminescent lithium fluoride.

The relative light output per Gy in polystyrene for roentgen beams of 6 and 42 MV and electrons between 2.2 and 34.5 MeV relative to 60Co gamma radiation is reported for different kinds of LiF dosemeters. The distribution of the absorbed dose inside a 0.25 and 0.4 mm thick LiF-teflon disc surrounded by polystyrene and irradiated with 60Co, 42 MV roentgen radiation and 39 MeV electrons was measured using 0.01 and 0.02 mm thick Lif-teflon discs. The measurements show that the absorbed dose distribution in the dosemeter depends on the energy of the radiation. When flat dosemeters were used, differences between the signals measured at the two orientations possible during read-out could easily amount to several per cent, and for this reason 0.4 mm and 0.5 mm LiF-Teflon discs were not trusted when the highest accuracy was required. The cavity theory by Burlin does not account for the phenomena caused by differences in electron scattering properties of the dosemeter and the phantom material. Some suggestions are presented for a different cavity theory for flat dosemeters dealing also with these phenomena. It describes the results to about the same degree of approximation as the Burlin theory, and fails to explain the observed energy dependence for electrons.

Reproducibility of field alignment in radiation therapy. A large-scale clinical experience.

A specially designed cassette which gives an excellent quality of portal films has been used to determine the set-up accuracy and uncertainties in treatment alignment during full-course radiation therapy on patients treated for some common malignant diseases. An analysis of a comparison between simulator films and portal films is also presented. For various diagnoses treatment-to-treatment positioning varied with an average standard deviation of 3.5 mm despite the use of laser alignment and good patient fixation.

99Tcm-solcocitran in the detection of bone malignancy.

A new 99Tcm-labelled compound, 99Tcm-Solcocitran, has been introduced for detection of bone and brain malignancy. It is claimed to be specific for neoplastic tissue. In the present material, however, 99Tcm-Solcocitran was less sensitive in indicating metastatic bone lesions in patients than was 99Tcm-Diphosphonate or conventional radiography. Both 99Tcm compounds accumulated in fractures in dogs. 99Tcm-Solcocitran seems to offer no advantage over existing techniques in the detection of bone malignancy.

Improved portal film image quality in radiation therapy with high energy photons.

Various metal screen-film combinations have been investigated in order to determine the best radiographic image. The quality of these different combinations has been evaluated by measuring the scattered to primary film dose ratio S/P. The S/P ratio increases with increasing atomic number of the front screen for 4 MV x-rays but shows no significant difference for 8 MV x-rays. For rear screens the S/P ratio is slightly increased for higher atomic numbers. A metal with an atomic number around 26-29 should be an optimal metal screen regarding quality aspects. A cassette of stainless steel has, in clinical use for portal and/or verification films, given very good images.

Dose- and time-response for breast cancer risk after radiation therapy for benign breast disease.

Exposure of the breast to ionising radiation increases the risk of breast cancer, especially among young women. However, some issues remain controversial, for instance the shape of the dose-response curve and the expression of time-related excess. The main purpose of this report was to examine the dose-response curves for radiation-induced breast cancer formulated according to radiobiological target theories. Another purpose was to analyse the time-related excess of breast cancer risk after exposure when dose and age at first exposure were held constant. Breast cancer incidence was analysed in a cohort of 3090 women diagnosed with benign breast disease during 1925-61 (median age 37 years). Of these, 1216 were treated with radiation therapy. The dose range was 0-50 Gy (mean 5.8 Gy). The incidence rate as function of dose was analysed using a linear-quadratic Poisson regression model. Cell-killing effects and other modifying effects were incorporated through additional log-linear terms. Additive and multiplicative models were compared in estimating the time-related excess. The analysis, which was based on 278 breast cancer cases, showed a linear dose-response relationship at low to medium dose levels with a cell-killing effect of 5% Gy-1 (95% confidence interval 2-9%). For a given absorbed dose and age at first exposure the time-related excess was proportional to the background rates with a suggestion that the excess remains throughout life.

Analysis of postoperative vaginal vault radiotherapy of stage I endometrial cancer with different radionuclides.

A total of 213 patients in stage I grade 1 endometrial cancer were treated postoperatively with either radium or caesium vaginal applicators. The rate of complication and the incidence of second malignancies were studied in both groups. The frequency of grades 2 and 3 vaginal complications was higher among patients treated with caesium applicators but not statistically significant. The observed number of second malignancies was significantly higher than expected in the radium-treated group, in which the observed number of second malignancies with distant location was also significantly higher than expected, which could not be found in the caesium group.

Bone scanning with 99Tcm compounds in metastasizing mammary carcinoma.

A comparison of three compounds for bone scanning has been carried out in 9 patients with metastatic mammary carcinoma for evaluating their effectiveness. The best results were obtained with 99Tcm diphosphonate. For the other two compounds tested, 99Tcm polyphosphate and 99Tcm pyrophosphate, no difference could be demonstrated.

Tumors after radiotherapy for thyroid cancer. A case-control study within a cohort of thyroid cancer patients.

A case-control study of Swedish thyroid cancer patients was conducted to evaluate the possible influence of 131I treatment and external radiotherapy on the risk of developing a subsequent cancer. Both cases and controls derived from a cohort of Swedish thyroid cancer patients treated with 131I (n = 834) or by other means (n = 1,121). Thirty-six breast, 13 stomach, 12 kidney, and 5 bladder cancers were found more than 2 years after 131I treatment/thyroid cancer diagnosis. Individual, absorbed dose in the organs was calculated by using ICRP tables, administered activity of 131I, and 24-h 131I uptake. In studying the effect of 131I and external radiotherapy no statistically significant dose-response relationships were found for cancers of the breast, stomach, bladder or kidney. When the absorbed dose from 131I was analyzed separately the risks remained essentially the same. The present follow-up time and the relatively low absorbed dose that the patients received from 131I and external radiotherapy necessitate studies with a longer follow-up time or a larger patient material before more firm conclusions can be made.

Six-year recurrence free survival after intraluminal iridium-192 therapy of human bilobar biliary papillomatosis. A case report.

BACKGROUND: Biliary papillomatosis is rare and often fatal. Liver resection or transplantation is recommended but may be impossible due to tumor or patient factors; furthermore, it appears to the authors of this study that no follow-up results after transplantation have been reported in previous studies. METHODS: Bilobar but limited biliary papillomatosis in a man age 54 years was mapped by cholangiopancreatography, cholecystectomy, and operative cholangioscopy. After cholangioscopic electrocoagulation, iridium-192 wires were temporarily inserted into the affected bile ducts, giving a dose of 60 grays at a 3-mm distance. Another percutaneous cholangioscopic electrocoagulation was performed 3 weeks later. RESULTS: The patient has been free of tumor and in good health for 80 months, but he has a long term stenting of a nonneoplastic stricture at the confluence of the bile ducts. CONCLUSIONS: Mechanical tumor reduction and intraluminal brachytherapy could possibly replace transplantation (which up to now has been suggested but not reported) when this life-threatening disease is bilobar, and also possibly replace liver resection for limited tumors in patients who are too frail for surgery.