Bone sarcoma

Jee WSS, Dell RB, Parks NJ, et al. 1985. Toxicity of plutonium and americium Relationship of bone composition to location of 226Ra, 239Pu and241 Am induced bone sarcomas. EUR 9250 155-174. 

Judson I, Radford JA, Harris M, et al. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL(R)/CAELYX(R)) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma, a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2001 37 870. 

Leahy M, Ray-Coquard 1, Verweij J, Le Cesne A, Duffaud F, Hogendoom PC, Fowst C, de Balincourt C, di Paola ED, van Glabbeke M, Judson 1, Blay JY. (2007) European Organisation for research and treatment of cancer soft tissue and bone sarcoma group. Ear J Cancer 43 308-315. 

Following intravenous injection of Thorotrast in humans and animals, various malignancies were found, primarily liver cancers (latency period of 25-30 years), leukemia (latency period of 20 years), and bone cancers (latency period of about 26 years). Short-lived daughter products of thorium also resulted in the induction of bone sarcoma because of their short radioactive half-lives. Intravenous injection of thorium-228 resulted in dose-dependent induction of bone sarcoma in dogs (Lloyd et al. 1985 Mays et al. 1987 Stover 1981 Wrenn et al. 1986). At the highest administered level, the animals died from systemic radiological effects (e.g., radiation induced blood dyscrasia and nephritis) before the bone sarcoma could develop (Stover 1981 Taylor et al. 1966). A relationship was found between the amount of thorium-227 (half-life of 18.7 days) injected intraperitoneally and the incidence of bone sarcoma in mice (Luz et al. 1985 Muller et al. 1978). 

Lloyd RD, Wrenn ME, Taylor GN, et al. 1985. Toxicity of Ra and Th relative to Ra for bone sarcoma induction in beagles. Strahlentherapie [Sonderb] 80 65- 69. 

It is indicated in GI tract carcinoma, acute myeloblastic leukaemia, bronchogenic, breast and ovarian carcinoma, soft tissue and bone sarcomas, malignant lymphoma primary management of nonmetastatic bladder carcinoma (intravesical administration), Wilm s tumor and neuroblastoma. 

The BEIR III risk estimates formulated under several dose-response models demonstrate that the choice of the model can affect the estimated excess more than can the choice of the data to which the model is applied. BEIR III estimates of lifetime excess cancer deaths among a million males exposed to 0.1 Gy (10 rad) of low-LET radiation, derived with the three dose-response functions employed in that report, vary by a factor of 15, as shown in Ikble 6.1 (NAS/NRC, 1980). In animal experiments with high-LET radiation, the most appropriate dose-response function for carcinogenesis is often found to be linear at least in the low to intermediate dose range (e.g., Ullrich and Storer, 1978), but the data on bone sarcomas among radium dial workers are not well fitted by either a linear or a quadratic form. A good fit for these data is obtained only with a quadratic to which a negative exponential term has been added (Rowland et al., 1978). 

The important inorganic toxic compounds to be considered in the following pages are arsine, arsenic trichloride, white arsenic, arsenites and arsenates and arsenic sulphides. Metallic arsenic itself is not poisonous, and the intravenous injection of a colloidal solution of this substance has been found 8 to benefit greatly a case of bone sarcoma of the femur which did not respond to X-ray treatment. 

Based on their findings, bone sarcomas, carcinomas of the perinasal sinuses and mastoid air cells (often called head cancers), and deterioration of skeletal tissue are considered to be the only effects that are unequivocally attributable to internal radium (Rundo et al. 1986). 

These bone sarcomas and head carcinomas have been seen in many radium dial painters and have appeared from 5 to more than 50 years after first exposure to radium. Of those dial painters for whom radium intakes have been estimated (a total of 1,907), 41 have developed bone sarcomas,... 

Of the Elgin State Hospital patients who received injections of radium-226 (see Section 2.2.4), two patients developed bone sarcomas, four developed head carcinomas, and a seventh patient had both types of malignancy (statistical significance was not addressed) (Gustafson and Stehney 1985). 

Cancer. In humans, radium-224 is known to induce bone sarcomas, and it is strongly suspected of inducing breast cancer in females who received this isotope when younger than 21 years of age at total doses greater than 12 pCi/kg (444 kBq/kg). Liver and kidney cancers are also possibly induced by radium-224 (Spiess et al. 1989). 

Chmelevsky D, Kellerer AM, Spiess H, et al. 1985. A proportional hazards analysis of bone sarcoma rates in German radium patients. Strahlentherapie [Sonderb] 80 32-37. 

Chmelevsky D, Kellerer AM, Land CE, et al. 1988b. Time and dose dependency of bone-sarcomas in patients injected with radium-224. Radiat Environ Biophys 27 103-114. 

Mays CW, Speiss H. 1984. Bone sarcomas in patients given radium-224. In Boice JD, Fraumeni JF, eds. Radiation carcinogenesis epidemiology and biological significance. N.Y. Raven Press, pp 24-1252. 

Mays CW, Spiess H Chmelevsky D, et al. 1985a. Bone sarcoma cumulative tumor rates in patients injected with Ra. Strahlentherapie [Sonderb] 80 27-31. 

Schlenker RA, Keane AT, Unni KK. 1989. Comparison of radium-induced and natural bone sarcomas by histologic type, subject age and site of occurrence. Br J Radiol 21 55-62. 

Wrenn ME, Taylor GN, Stevens W, et al. 1986. Summary of dosimetry, pathology, and dose response for bone sarcomas in beagles injected with radium-226. In Thompson RC, Mahaffey JA, eds. Life span radiation effects studies in animals What can they tell us Washington, DC U.S. Department of Energy, Office of Scientific and Technical Information. CONF-830951. 

Tucker MA, D Angio GJ, Boice JD, Strong LC, Li FP, Stovall M, Stone BJ, Green DM, Lombardi F, Newton W (1987) Bone sarcomas linked to radiotherapy and chemotherapy in children. N Engl J Med, 317 588-593. 

Osteogenic Sarcoma. Cisplatin figures prominently in the treatment of primary bone sarcomas. Single-agent response rates approximate 30% in... 

No evidence linking oral exposure to uranium to human cancer has been found. Although natural, depleted, or enriched uranium and uranium compounds have not been evaluated in rodent cancer bioassays by any route by the NTP (BEIR 1980, 1988, 1990 Hahn 1989 Sanders 1986 UNSCEAR 1982,1986,1988), there is potential for the carcinogenicity of uranium, since it emits primarily alpha radiation. Nevertheless, no evidence has been found to associate human exposure to uranium compounds and carcinogenesis. The National Academy of Sciences has determined that bone sarcoma is the most likely cancer from oral exposure to uranium however, their report noted that this cancer has not been observed in exposed humans and concluded that exposure to natural uranium may have no measurable effect (BEIR IV). 

The report estimated a lifetime risk of excess bone sarcomas per million people of 1.5 if soluble uranium isotopes were ingested at a constant daily rate of 1 pCi/day (0.037 Bq/day). The number of bone sarcomas that occur naturally in a population of a million people is 750. However, no quantitative risk coefficient estimates for developing human exposure protection benchmarks were provided in this report. In addition, the BEIR IV analysis was presumably based on generic short-lived alpha-emitting sources, such as radon that have a higher potential for inducing cancer, and not on radionuclides with relatively longer radioactive half-lives like and Perhaps more importantly, the BEIR IV report... 

Spiess FW, Mays CW. 1973. Protraction effect on bone sarcoma induction of Ra 224 in children and adults. In Sanders CL, et al., ed. Radionuclide carcinogenesis. Springfield, VA NTIS, 437-150. 

Ifosfamide is an alkylating agent belonging to the group of oxazaphosphorines. It is used to treat a variety of solid tumors in children, including rhabdomyosarcoma, soft tissue sarcomas, Wilms tumor, bone sarcomas, and neuroblastoma, and leukemias and lymphomas in adults. It is also sometimes used in combination with other drugs, such as doxorubicin or cisplatin and etoposide. 

Debiec-Rychter M, Dumez H, Judson I, et al. Use of c-KIT/ PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal ttrmottrs entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2004 40 689-695. 

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