Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor.

BACKGROUND: We sought to investigate the characteristics and survival rate of patients with gastrointestinal stromal tumor (GIST) associated with other primary malignancies. PATIENTS AND METHODS: A total of 783 patients with GIST were identified from 1995 to 2007. Additional primaries included tumors not considered metastasis, invasion, or recurrence of GIST, nor non-melanoma skin cancer. Data on gender, age at diagnosis, follow-up time after diagnosis, and death were collected. RESULTS: Of the 783 patients with GIST, 153(20%) were identified with at least one additional primary. Patients with additional primaries were more often men (M : F 1.5 versus 1.3) and older (66 versus 53 years). More patients had another cancer diagnosed before (134) than after (52) GIST. Primaries observed before GIST were cancers of the prostate (25), breast (12), esophagus (9), and kidney (7) and melanoma (6). Lung (5) and kidney (5) primaries were the most frequent after GIST. The 5-year survival was 68% for patients with primaries before GIST, 61% for patients with primaries after GIST, 58% for patients with GIST only, and 49% for patients with two or more primaries in addition to GIST (P = 0.002). CONCLUSIONS: Approximately 20% of patients with GIST develop other cancers. Inferior median 5-year survival was observed in patients with GIST with two or more other cancers. The etiology and clinical implications of other malignancies in patients with GIST should be investigated.

Of mice and men: divergent risks of teriparatide-induced osteosarcoma.

SUMMARY: Since approval by the U.S. Food and Drug Administration (FDA) in December 2002, teriparatide (recombinant 1-34 PTH; Forteo) has been safely used by more than 430,000 patients. Prior to FDA approval, however, there was concern that teriparatide might increase the risk for patients to develop osteosarcoma, as almost 45% of the rats treated with this drug at the highest-tested dose level developed this aggressive form of bone cancer. Balancing the proven benefits of teriparatide shown by clinical trials with the theoretical risk for teriparatide-induced human osteosarcoma, the FDA mandated both a 'black-box' warning of this potential side-effect and a company-sponsored postmarketing surveillance program. As a participating institute of that surveillance program, we report upon the second person with potential teriparatide-induced osteosarcoma, in this case, complicated by a history of pelvic radiation. INTRODUCTION: Given the theoretic risk of the drug teriparatide and the known risk of radiation in inducing osteosarcoma, we raise the issue of whether teriparatide magnified the risk of radiation-induced osteosarcoma in our patient and try to determine which factor played the predominant role in the development of his disease. METHODS: We analyzed preclinical rat data, human clinical experience with teriparatide, and our patient's clinical history to assess the human risk of teriparatide and radiation exposure. RESULTS: After the first case of suspected osteosarcoma was reported in December 2005, we encountered a second possible teriparatide-induced osteosarcoma less than a year later. Review of the preclinical animal data would suggest that teriparatide is safe for human use when used as recommended by the manufacturer. Given the location of the sarcoma within the field of radiation and the limited exposure to teriparatide before diagnosis, it is unlikely that teriparatide played the predominant role in the emergence of this patient's osteosarcoma. We cannot, however, exclude the possibility that teriparatide magnified the carcinogenic effect of radiation therapy to induce the osteosarcoma. CONCLUSION: Of more than 430,000 persons who have received teriparatide for treatment of severe osteoporosis, we report the second patient to develop osteosarcoma. Although teriparatide reduces osteoporosis-related fractures in select patient populations, important contraindications, such as prior radiation exposure, should be considered before use.

Modelling the resilience of Australian savanna systems to grazing impacts.

Savannas occur across all of northern Australia and are extensively used as rangelands. A recent surge in live cattle exports to Southeast Asia has caused excessive grazing impacts in some areas, especially near watering points. An important ecological and management question is "how resilient are savanna ecosystems to grazing disturbances?" Resilience refers to the ability of an ecosystem to remain in its current state (resist change) and return to this state (recover) if disturbed. Resilience responses can be measured using field data. These responses can then be modelled to predict the likely resistance and recovery of savannas to grazing impacts occurring under different climatic conditions. Two approaches were used to model resilience responses. First, a relatively simple mathematical model based on a sigmoid response function was used. This model proved useful for comparing the relative resilience of different savanna ecosystems, but was limited to ecosystems and conditions for which data were available. Second, a complex process model, SAVANNA, was parameterised to simulate the structure and function of Australian savannas. Simulations were run for 50 years at two levels of grazing to evaluate resistance and then for another 50 years with no grazing to evaluate recovery. These runs predicted that savanna grasslands were more resistant to grazing (changed less) than red-loam woodlands, which recovered relatively slowly from grazing impacts. The SAVANNA model also predicted that these woodlands would recover slightly slower under the climate change scenario projected for northern Australia.

Modelling the trade-off between fire and grazing in a tropical savanna landscape, northern Australia.

As savannas are widespread across northern Australia and provide northern rangelands, the sustainable use of this landscape is crucial. Both fire and grazing are known to influence the tree-grass character of tropical savannas. Frequent fires open up the tree layer and change the ground layer from perennials to that dominated by annuals. Annual species in turn produce copious quantities of highly flammable fuel that perpetuates frequent, hot fires. Grazing reduces fuel loads because livestock consumes fuel-forage. This trade-off between fire and grazing was modelled using a spatially explicit, process-orientated model (SAVANNA) and field data from fire experiments performed in the Victoria River District of northern Australia. Results of simulating fire (over 40 years) with minimal or no grazing pressure revealed a reduction in the shrub and woody plants, a reduction in grasses, and no influence on the tree structure given mild fires. While mature trees were resistant to fire, immature trees, which are more likely associated with the shrub layer, were removed by fire. The overall tree density may be reduced with continual burning over longer time periods because of increasing susceptibility of old trees to fire and the lack of recruitment. Increases in stocking rates created additional forage demands until the majority of the fuel load was consumed, thus effectively suppressing fire and reverting to the grazing and suppressed fire scenario where trees and shrubs established.

Desertification in Australia: An eye to grass roots and landscapes.

Desertification in some form is estimated to have occurred over about 42% of the 5 million km(2) of arid and semiarid lands in Australia. The most common form of desertification is loss of perennial grasses from grasslands, savannas, and open woodlands, often with a replacement by inedible shrubs. Desertification continues to be a problem, especially during droughts when grazing pressures reduce ground cover, laying bare landscapes to wind and water erosion. But two national programs, Drought Alert and Landcare, are giving new hope in controlling land degradation. Both use a grassroots approach by promoting action through local pastoralist and farmer groups and by encouraging the use of effective techniques for rehabilitating landscapes. A strategic application of ponding banks and contour traps with an eye to the landscape has proven successful in stopping and reversing desertification processes.