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Tarnished adornment: The troubled history of Québec's institut du radium.

In 1922 the Québec government appropriated $100,000 for the purchase of radium to found an Institut du Radium at the University of Montreal. Opened largely through the initiative and drive of Dr. Joseph-Ernest Gendreau, the institut was the first organization devoted to radium therapy and cancer treatment in Canada. This paper describes the background, origins and development of the Institut with a focus on the medical, political, and cultural factors which led to its establishment. From the point of view of the Québec government, the Institut was a way of showing its commitment to health care, of strengthening cultural bonds with France, and of demonstrating the province's emerging technological prowess. Radium was to be an adornment which showed off the scientific advancement of 20th century Québec. Unfortunately, the Institut never achieved the scientific or cultural stature promised by the rhetoric. Which surrounded its opening, and this paper will examine the factors which led to its instability and eventual demise. In addition to an overwhelming clinical workload, chronic underfunding and geographic isolation, the Institut fell victim to medical politics. Its success was undermined by opposition from medical groups and competition from hospitals which led to the establishment of multiple radium centres in Montreal. A fundamental problem was confusion over whether its role should be a research institute, a general medical clinic, or a specialized cancer centre. Despite numerous financial and administrative crises and the severing of its academic affiliation in 1945, the Institut survived until 1967. Despite its troubled history, the Institut made an important contribution to Canadian medicine through its ground braking role in the establishment of radiotherapy and cancer treatment. In addition, the lessons learned from its difficulties proved useful to other provinces planning their own cancer programs.

Academies and Institutes↗

[Exclusive radiotherapy (cobalt teletherapy-radium therapy) in epithelioma of the uterine cervix. 400 cases treated between 1959 and 1969].

The author presents results of 420 cases of epithelioma of the cervix of the uterus treated between 1959 and 1969, using exclusively physical agents such as cobalt therapy and radium therapy. 399 cases are analysed. 9 patients could not be traced and 12 died intercurrently. We have adopted the 1969 U.I.C.C. classification. External irradiation alwyas preceded radium therapy and its importance varied according to the stage: however, doses of 2,000 to 5,000 rads were used at the rate of 1,000 rads weekly for two to five weeks; this was followed by classical radium therapy (Paris method) with colpostat and uterine sound. The number of mgh was consequently reduced and the dose administered was inversely proportional to that of the external irradiation. On the whole, tolerance was good in this type of treatment. Complications were mainly limited to a few minor intestinal disorders; in belated sequelae, these disorders were not more than those usually noted. Results after five years reveal only one death out of 19 for stage T1 lesions. Recoveries are distributed as follows: 72 out of 93 stage T2a lesions (77%), 46 out of 87 stage T2b lesions (53%), 54 out of 131 stage T3a lesions (41%) and 13 out of 46 stage T3b lesions (28%). However, results according to period are better. For the 1967 to 1969 period, results were 92%, 62%, 53% and 30% for stages T2a, T2b, T3a and T3b respectively. Improvement in results could be due to external irradiation. This sterilizes pelvic macroscopic or microscopic extensions and decreases inflammatory phenomena and the volume of the cervix of the uterus. These changes facilitate radium therapy which remains an indispensable arm for sterilizing primary lesions. The author compares his results with those of the literature. He develops arguments for techniques which associate external irradiation and radium therapy in a well defined order. These techniques are particularly important for stages T2b or T3 in which lymph gland lesions are common and where doses of about 5,000 and 6,000 rads are necessary for sterilization. Possibilities of improving future results are analysed. Particular attention should be paid to the lumbo-aortic volume; lymph gland metastasis are frequent here and should be treated continuously with the pelvic volume.

Cobalt Radioisotopes↗

[Primary combined radiotherapy of carcinoma of the uterine cervix. Comparison of 192Ir with radium].

A retrospective study of primary irradiated carcinomas of the uterine cervix was made in order to compare the effect of radium with the effect of a 192Ir afterloading therapy with high dose rate which had been introduced 2 1/2 years before. A group of 31 patients treated with iridium was opposed to a historical control group of 24 patients treated with radium. Both groups were submitted to the same method of simultaneous percutaneous irradiation. All consecutively treated patients exposed to a percutaneous focal dose of greater than 45 Gy were evaluated. The iridium and radium doses applied as well as the values measured in intestine and bladder are presented. The iridium group had the same or a slightly less favorable prognosis (prognostic factors compared: stage, percutaneous dose, histology, age) than the radium group. The remission rates were identical for both therapy methods. Patients treated with iridium have a slightly better curve of recurrence-free interval and survival time, even taking into consideration the shorter observation period. Two out of the patients treated with iridium and four out of those treated with radium presented severe long-term side effects with formation of fistulas (average incidence 12,5 months and 12,7 months after the beginning of therapy, respectively).

Brachytherapy↗

[Experience with the conversion from radium therapy to an afterloading procedure with special reference to spatial dose distribution].

In radium therapy, the spatial and temporal dose distribution have never been identical in the different hospitals. However, the healing results did not vary correspondingly despite the partly great methodical differences between German and foreign hospitals. Furthermore, the spatial and temporal dose distribution in radium therapy did not conform to theoretic considerations but were a result of the low specific activity of radium as well as of the technical standard of X-ray therapy units until the sixties. It is shown that all requirements valid for radium therapy are also fulfilled by the afterloading method using a linear ray emitter, if an adequate dosage and fractionation is chosen. Taking into account the radiation risk, we think that the radium must be replaced by an afterloading method using a less dangerous nuclide. In our opinion the high dose rate technique is the most favorable method.

Brachytherapy↗

Association of leukemia with radium groundwater contamination.

Radiation exposure, including the ingestion of radium, has been causally associated with leukemia in man. Groundwater samples from 27 counties on or near Florida phosphate lands were found to exceed 5 pCi/L total radium in 12.4% of measurements. The incidence of leukemia was greater in those counties with high levels of radium contamination (greater than 10% of the samples contaminated) than in those with low levels of contamination. Rank correlation coefficients of .56 and .45 were observed between the radium contamination level and the incidence of total leukemia and acute myeloid leukemia, respectively. The standardized incidence density ratio for those in high-contamination counties was 1.5 for total leukemia and 2.0 for acute myeloid leukemia. Further investigation is necessary, however, before a causal relationship between groundwater radium content and human leukemia can be established.

Florida↗

[Revision of the radium isodose atlas of Göttingen with a new calculation method].

The Radium Isodose Atlas of Göttingen was recalculated after having established a new computer program for the determination of dose distributions around intracavitary radium inserts. The program takes into consideration the complicated structure of the radium applicators type Buchler. The exactness of the program was checked by computing known radium sources and by detailed measures. The calculated dose values were reduced by 30% on an average with respect to the original measurements. This difference is explained mainly by the dependence on energy of the Cds dosimeter used at that time (1959). The clinically evaluated dose has not been changed (identical milligram element hours), however, a comparison of radium doses with other hospitals and with an additional percutaneous irradiation has become possible by the recalculation. Point A has been redefined according to international practice.

Brachytherapy↗

Radium in drinking water and the risk of death from bone cancer among Ontario youths.

OBJECTIVE: To determine whether residents of Ontario who are exposed to radium 226 naturally occurring in drinking water are at increased risk of bone cancer. DESIGN: A population-based case-control study of records from death and birth registries. Water samples were obtained from residences at the time of birth and of death. SETTING: Ontario. PARTICIPANTS: All Ontario-born people under the age of 26 years who died of bone cancer between 1950 and 1983. Control subjects were those who died of any other disease matched by age, sex and year of death. OUTCOME MEASURES: Radium exposure distributions and estimation of risk. RESULTS: An association was found between death from bone cancer and exposure to radium at the birthplace residence in concentrations of 7.0 mBq/L or more (odds ratio 1.58, 90% confidence interval [CI] 1.01 to 2.50; p = 0.047). There was a statistically significant exposure-response relation (p = 0.045). The increase in risk was similar for the main types of childhood bone cancer: osteosarcoma, Ewing's sarcoma and chondrosarcoma. CONCLUSIONS: The estimated risk at these exposure levels is much higher than would be predicted. The association may be spurious, the point estimates of risk may be too high, or risk factors derived from other exposure circumstances may not be valid for exposure to radium beginning in the prenatal period. Should the findings be confirmed, consideration might be given to removing radium from drinking-water sources.

Adolescent↗

Use of prophylactic antibiotics in patients with carcinoma of the cervix receiving intracavitary radium insertion.

The efficacy was studied of prophylactic antibiotics in preventing febrile morbidity in patients with carcinoma of the cervix undergoing intracavitary radium insertions. Of 93 consecutive patients who had completed external irradiation and two intracavitary radium insertions, 63 (67.74%) had fever over 37.5 degrees C and 19 (20.43%) had fever over 38 degrees C during radium insertion when prophylactic antibiotics were not given. When 3 gm cefoxitin was given over 24 hrs in divided doses as prophylaxis, 39 (41.93%) had fever over 37.5 degrees C and 8 (8.60%) had fever over 38 degrees C. The difference was found to be statistically significant for fever over 37.5 degrees C (p < 0.001) and fever over 38 degrees C (p < 0.05). There was no difference in the duration of fever in the two groups, but the use of antibiotic prophylaxis apparently decreased the need for subsequent therapeutic antibiotics from 13.98% to 4.30%. No difference in the febrile incidence was found when considering the size of the cervical tumour, the stage of the disease, or whether it was a first or second radium insertion, or whether the patient had her menopause already. Prophylactic antibiotics were also found to be more effective in preventing febrile morbidity over 37.5 degrees C in those receiving adjuvant chemotherapy as compared to the general study group (p < 0.025). We concluded that the use of prophylactic antibiotics has beneficial effect in decreasing febrile episodes during the period the radium was inserted, as well as in reducing subsequent need for therapeutic antibiotics, while its use in immunocompromised patients who are prone to sepsis may also be of advantage.

Adult↗

[Effectiveness and safety of radium chloride in the treatment of ankylosing spondylitis. Results of an observational study].

After radium chloride was approved for the therapy of ankylosing spondylitis (AS) in Germany on October 23, 2000, an open, non-comparative prospective observational study was planed. The assessment involved 308 patients with the diagnosis of AS and radiological evidence of spinal involvement who were treated with at least one injection of radium chloride. 278 of these patients received the full cycle of 10 injections (a total of 10 MBq radium-224) one injection one per week for a period of 10 successive weeks. Validated outcomes were measured before therapy and six months after therapy according to the recommendations of the "assessment in ankylosing spondylitis working group"(ASAS). The primary endpoint was disease activity assessed using the BASDAI ("Bath Ankylosing Spondylitis Disease Activity Index"). Secondary endpoints included the BASFI ("Bath Ankylosing Spondylitis Functional Index"), as well as self-reported pain and global patient ratings. Patients showed significant improvement in all of the parameters assessed (BASDAI, BASFI, pain, global patient rating) at 6-months post-treatment. At this time, the mean BASDAI and BASFI scores improved from 5.5 to 3.5 and from 5.6 to 3.7, respectively. Pain decreased from a mean of 7.3 to 4.1, and disease activity (as rated by patients) also decreased from 7.2 to 4.1 (p < 0.001 for all of them). Drug tolerance was good. Six adverse events were documented, none of which was serious and none led to discontinuation of treatment. According to the data provided here medical treatment with radium chloride seems to be effective and safe during an observation period of 6 months. Nevertheless, a randomized placebo-controlled study should be performed in the near future in order to safeguard the level of evidence.

Adult↗

Analysis of the severe complications of irradiation of carcinoma of the cervix: whole pelvis irradiation and intracavitary radium.

From January, 1967 to December, 1974, 325 patients with carcinoma of the uterine cervix were treated with a minimum of 4,000 rad whole pelvis irradiation plus intracavitary radium. These patients had large, sometimes massive, tumors. Generally, the larger the primary tumor the greater the amount of external irradiation delivered, with an appropriate reduction in the amount of intracavitary radium. Patients who had a positive lymphangiogram or a pre- or postirradiation hysterectomy or lymphadenectomy are not included in this analysis. All patients were followed for a minimum of 5 years. Local and regional failure rate in 193 patients receiving 4,000 rad whole pelvis irradiation plus radium was 1% and 4%, respectively, with a 3.1% incidence of severe complications. In 111 patients who received 5,000 rad whole pelvis irradiation plus radium, the local and regional failure rate was 3.5% and 4.5%, respectively, with a 10% incidence of severe complications. In patients who received 5,000 rad whole pelvis irradiation, complications were associated with unilateral parametrial boosts and with protruding vaginal sources. Of 21 patients who received 6,000 rad whole pelvis irradiation, three patients developed fistulae associated with high doses to the vagina delivered with protruding vaginal sources.

Brachytherapy↗

Distribution of radium in oil and gas industry wastes from Malaysia.

Radium concentrations in 470 samples of the various types of waste from oil and gas industries were analysed using gamma spectrometers. The results showed that the radium concentration varied within a wide range. The highest mean 226Ra and 228Ra concentrations of 114,300 and 130,120 Bq/kg, respectively, were measured in scales. Overall, 75% of the waste, mostly sludge and extraction residue lies within the normal range of radium concentration in soils of Malaysia. However, some platform sludge can have radium concentration up to 560 Bq/kg.

Industrial Waste↗

Source of radium in a well-water-augmented Florida lake.

A study of the lake waters of Saddleback Lake, Florida was undertaken with the goal of determining the source of elevated radium activities in the lake. Four radium isotopes, (226)Ra, (228)Ra, (223)Ra and (224)Ra, were measured and activities of all the four radium isotopes were substantially greater in the well water used to augment the lake as compared to the lake waters. In the surface water, radium activities were highest close to the well used for augmentation in the initial sampling. Activities initially decreased with time after augmentation from the well ceased. The (223)Ra/(226)Ra activity ratio decreased during the first month of sampling and closely followed an exponential decay curve based on the (223)Ra decay constant. Trends in the activities and the (223)Ra/(226)Ra activity ratios support the conclusion that the well used to augment the lake was the dominant source of (223)Ra and (226)Ra to Saddleback Lake during this study. The (224)Ra/(226)Ra activity ratio did not follow the expected trend of exponential decay based on the (224)Ra decay constant. While the augmentation well supplied some (224)Ra, these results suggest that there must be an additional source of (224)Ra to the lake. The most likely additional source of (224)Ra appears to be the ingrowth of (224)Ra on the sediment within the lake from (228)Ra (via (228)Th).

Florida↗

Determination of radium-226 in aqueous solutions by alpha-spectrometry.

The new European legislation imposes a lower threshold for radioactivity in drinking water. This requires the development of more sensitive and reliable analytical methods. This work presents an improved alpha-spectrometric technique to determine the radium-226 activity in aqueous solution relying on the radium adsorption onto a thin manganese oxide layer followed by alpha-measurement. The preparation of the MnO2 deposit has been optimized as well as the radium adsorption conditions. Detection threshold and limit of 5 and 10 mBq x L(-1), respectively, with a 10% (95% confidence) uncertainty are currently reached. This paper reports on the overall technique and on its application to assess the radium-226 activity in 28 French mineral waters. In addition, the gross alpha- and beta-activities have been evaluated using proportional counting while the uranium concentrations were derived from ICPMS.

Algorithms↗

The metabolism of radium in dairy cows.

1. The isotopes (45)Ca and (224)Ra were administered simultaneously, both orally and intravenously, to two pairs of cows. 2. The first pair of animals received large doses of (224)Ra and (45)Ca, which produced clinical and metabolic disturbances. 3. The second pair of animals received much smaller doses and showed no clinical disturbances. The mean recoveries in these animals of (45)Ca and (224)Ra in the 8 days after the oral administration were respectively: from faeces, 63.2 and 103.8%; from urine, 0.26 and 0.44%; from milk, 15.8 and 0.35% of the dose; and in the 8 days after intravenous administration: from faeces, 20.5 and 36.5%; from urine, 1.56 and 17.6%; from milk, 49.3 and 11.8% of the dose. 4. Calculation of discrimination factors shows that absorptive discrimination played the most important part in the overall discrimination between the calcium and radium in their passage from diet to milk, but that mammary discrimination plays a more important role than in the overall discrimination between calcium and strontium or barium. 5. In its treatment by the kidney radium is more like strontium than barium, but radium is actively secreted by the gut in the same way as barium. 6. In its skeletal metabolism radium is indistinguishable from calcium and strontium except in its rate of resorption, which is similar to that of barium.

Animals↗

[Long-term results of radium contact irradiation of laryngeal carcinoma and their relevance in modern therapeutical regimens].

BACKGROUND: Despite the fact that it is widely accepted that a second radiogenic carcinoma might occur after radiotherapy of laryngeal carcinomas, there are only a few long-term follow-up studies published yet. METHODS: Between 1973 and 1988 193 patients have been treated by radium contact irradiation because of glottic cancer (Tcis, T1, T2). After the cancer had been diagnosed by biopsy, a partial resection of the thyroid cartilage in the shape of a window 16 x 18 mm was carried out and a self-retaining capsule which harbours the radium was brought into position. RESULTS: 190 (181 men and 9 women) out of 193 patients could be followed up. At the time of investigation 109 patients had already died, 66 intercurrently. The actuarial disease free survival rate 5 and 10 years for Tcis/T1 glottic cancers were 84.6% and 83.6%. For T2 carcinomas a rate of 100% was found respectively. The actuarial overall survival rate was 96.8% after 5 and 93.1% after 10 years for Tcis/T1 carcinomas. The T2 carcinomas revealed an actuarial overall survival rate of 100% after 5 and 10 years. CONCLUSIONS: As the results of radium contact irradiation are not better than those which can be achieved by microsurgery or modern irradiation techniques no indication exists for a radium contact irradiation of glottic laryngeal cancer today.

Adult↗

A review of the potential for radium from luminising activities to migrate in the environment.

During the first half of the twentieth century, radium, mixed with other components, was used to luminise many items, including watches, clocks, dials and meters. On many sites, and in particular MoD sites, luminised instruments and paint were disposed of by burning and burial. This paper presents a review of the potential for radium from such sites to migrate in the environment. The most likely mechanisms of migration of radium from former luminising sites in the UK are surface-water erosion and transport, and the action of animals and people. Plant uptake or rainsplash followed by cropping of the plants is another possible mechanism, but the extent of impact is uncertain. The migration of significant quantities of radium through soils or rocks, or due to landsliding or wind transport, is considered to be of minimal importance to most UK sites. A low pH, high salinity (in particular of group II metals) or reducing groundwater would need to be present for migration through soils/rocks to occur and such conditions are unlikely to be present in most shallow aquifer systems in the UK. To reduce the potential for migration to occur it is recommended that luminising wastes at ground surface are removed or covered, that controls are put in place to limit animal activity and that human entry to former luminising sites is restricted.

Animals↗

Dose-response relationships for radium-induced bone sarcomas.

The incidence of bone sarcomas among 3055 female radium-dial workers who entered the dial industry before 1950 was used to determine dose-response relationships for the induction of bone sarcomas by radium. Two subpopulations were analyzed: all measured cases who survived at least 5 yr after the start of employment and all cases who survived at least 2 yr after first measurement. The first constituted a group based on year of entry; it contained 1468 women who experienced 42 bone sarcomas; the expected number was 0.4. The second comprised a group based on first measurement; it contained 1257 women who experienced 13 bone sarcomas; the expected number was 0.2. The dose-response function, I = (C + alpha D + beta D2)e-gammaD, and simplifications of this general form, were fit to each data set. Incidence (I) was in units of bone sarcomas per person-yr; (D) was the quantity (muCi) of radium that entered the blood. Two functions, I = (C + alpha D + beta D2)e-gammaD and I = (C + beta D2)e-gammaD, fit the data for year of entry (p greater than or equal to 0.05); both these functions and I = (C + alpha D) fit the data for first measurement. The function I = (C + beta D2)e-gammaD was used to predict the number of bone sarcomas in all other pre-1950 radium cases (medical, laboratory and other exposures); fewer were actually observed than the fit of this function to the female dial workers predicted.

Adult↗

Cells at risk for the production of bone tumors in radium exposed individuals: an electron microscope study.

The endosteal cells of bone from a 75-yr-old woman who had acquired radium internally, as a consequence of her previous employment as a radium dial painter, are documented here for the first time by electron microscopy. As a result of amputation for a fibrosarcoma in the region of the right knee joint, fresh samples of bone and tumor tissue from the femur were made available. A sample of bone, also obtained at amputation from an unirradiated control patient, age 65, was examined from the same site in the femur. A comparison of the bone-marrow interface from the two patients showed that, unlike the control bone where cells were seen close to bone mineral a fibrotic layer was interposed between the marrow cells and the bone mineral in the bone from the radium case. This layer varied in thickness up to 50 microns and was often acellular, although cell remnants and cells, which appeared viable, were sometimes seen within this layer. It is suggested that irradiation of those cells proliferating within, and at the edge of, this replacement fibrotic layer may be the most important in the induction of bone tumors rather than the original cells lying within the 0-10 microns range from bone mineral which has previously been supposed. The nuclear dimensions of the endosteal bone lining cells and their distance from bone mineral have been measured in the bones from the radium and control cases. These dimensions are important not only in understanding the mechanisms by which bone tumors arise but in developing models of carcinogenic risks of other alpha-particle emitting isotopes such as plutonium.

Aged↗