Bill Walsh Cancer Research Laboratories

Bill, Australia

Bill Walsh Cancer Research Laboratories

Bill, Australia
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Bromley R.,Northern Sydney Cancer Center | Bromley R.,University of Sydney | Oliver L.,Northern Sydney Cancer Center | Oliver L.,University of Sydney | And 3 more authors.
Medical Physics | Year: 2010

Purpose: Can the α and β values derived from uniform irradiation be used in the Summed Dose Method to predict cell survival for single or multiple fraction irradiation with a heterogeneous dose distribution? Method and Materials: A549 non‐small cell lung cancer cells were investigated by clonogenic assay in a NUNC 6‐well plate using single and multiple fractions up to 10Gy. The plate contains two uniformly irradiated wells and two heterogeneously irradiated wells. The α and β values measured in the uniformly irradiated wells were used to predict the survival for a sharp and shallow dose distribution. The experimental survival was compared with that predicted by the Summed Dose Method. Results: The Summed Dose Method cannot predict in the total well survival of A549 cells for either dose distribution at single fraction doses. The total well survival cannot be predicted for the sharp distribution at fraction 4 and 5, for any fraction in the irradiated region, for the shallow dose distribution at fractions 3 and 5 in the unirradiated region or any fraction in the irradiated region or total well. The Summed Dose Method can predict the survival of the sharp distribution at all single fraction doses in the unirradiated region and up to 2 Gy in the irradiated. The survival can be predicted at 5 Gy in the unirradiated region and 1 and 5 Gy in the irradiated for the shallow dose distribution. The survival is predicted at fractions 1, 2 and 4 in the unirradiated regions for the shallow dose distribution and is predicted for the sharp distribution at all multiple fractions in the unirradiated region, and fractions 1 to 3 in the total well. Conclusion: The Summed Dose Method is still limited in predicting cell survival for single or multiple fraction irradiation with a heterogeneous dose distribution. © 2010, American Association of Physicists in Medicine. All rights reserved.


Kao S.C.H.,Asbestos Diseases Research Institute | Harvie R.,Bill Walsh Cancer Research Laboratories | Harvie R.,University of Sydney | Paturi F.,Bill Walsh Cancer Research Laboratories | And 12 more authors.
Lung Cancer | Year: 2012

There is a need for new treatment strategies and prognostic markers for the management of malignant mesothelioma (MM). The activity of thalidomide/cisplatin/gemcitabine (arm A) or thalidomide alone (arm B) was investigated in two parallel phase II studies in patients with advanced MM, using 6 month progression free survival (PFS) as the principal end-point. The predictive role of pre-treatment and 8 week follow-up serum C-reactive protein (CRP), interlukin-6 (IL-6), interlukin-6 soluble receptor (sIL-6R), mesothelin (SMRP) and vascular endothelial growth factor (VEGF) was also assessed. The proportion of patients with stable disease for >6 months was similar in both studies (arm A 35%, arm B 29%) and toxicity was mainly grade I/II. In univariate analyses only pre-treatment VEGF and CRP were correlated with survival. At 8 weeks post treatment, increased survival was found with low (median) VEGF and CRP (P< 0.05). Change in VEGF over the first 8 weeks of treatment was also predictive for survival (P< 0.05). When pre-treatment VEGF was >median, decreasing VEGF was associated with increased survival (P< 0.05). In conclusion, thalidomide alone, or in combination with cisplatin/gemcitabine, controlled disease for >6 months in ∼30% of patients. Patients with decreasing VEGF during treatment had longest survival. Pre-treatment VEGF or CRP and early change in VEGF on treatment may predict treatment benefit and should be examined in future studies. © 2011 Elsevier Ireland Ltd.

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