Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management

Seasonal Movement and Distribution of Fluvial Adult Bull Trout in Selected Watersheds in the Mid-Columbia River and Snake River Basins

From 1997 to 2004, we used radio telemetry to investigate movement and distribution patterns of 206 adult fluvial bull trout (mean, 449 mm FL) from watersheds representing a wide range of habitat conditions in northeastern Oregon and southwestern Washington, a region for which there was little previous information about this species. Migrations between spawning and wintering locations were longest for fish from the Imnaha River (median, 89 km) and three Grande Ronde River tributaries, the Wenaha (56 km) and Lostine (41 km) rivers and Lookingglass Creek (47 km). Shorter migrations were observed in the John Day (8 km), Walla Walla (20 km) and Umatilla river (22 km) systems, where relatively extensive human alterations of the riverscape have been reported. From November through May, fish displayed station-keeping behavior within a narrow range (basin medians, 0.5–6.2 km). Prespawning migrations began after snowmelt-driven peak discharge and coincided with declining flows. Most postspawning migrations began by late September. Migration rates of individuals ranged from 0.1 to 10.7 km/day. Adults migrated to spawning grounds in consecutive years and displayed strong fidelity to previous spawning areas and winter locations. In the Grande Ronde River basin, most fish displayed an unusual fluvial pattern: After exiting the spawning tributary and entering a main stem river, individuals moved upstream to wintering habitat, often a substantial distance (maximum, 49 km). Our work provides additional evidence of a strong migratory capacity in fluvial bull trout, but the short migrations we observed suggest adult fluvial migration may be restricted in basins with substantial anthropogenic habitat alteration. More research into bull trout ecology in large river habitats is needed to improve our understanding of how adults establish migration patterns, what factors influence adult spatial distribution in winter, and how managers can protect and enhance fluvial populations