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Mckay M.J.,Divisions of Radiation Oncology | Mckay M.J.,Peter MacCallum Cancer Center | Mckay M.J.,Australian National University | Withana N.,Peter MacCallum Cancer Center | And 7 more authors.
Asia-Pacific Journal of Clinical Oncology | Year: 2011

Aims: Radiation therapy (RT) is used in the treatment of approximately half of all cancer patients. Although there have been great improvements in tumor localization and the technical accuracy of RT delivery, some RT patients still have idiosyncratic hypersensitivity to ionizing radiation (IR) in their normal tissues. Although much effort has been expended in the search for assays that could detect radiosensitive individuals prior to treatment and facilitate tailored therapy; a suitable and clinically practical predictive assay has yet to be realized. Since DNA double-strand breaks (DSB) are a major lesion caused by IR, we hypothesized that radiation hypersensitive individuals might be deficient in the repair of such lesions. Methods: To test this hypothesis we quantitatively and functionally characterized DSB repair of the two major non-homologous end-joining (NHEJ) sub-pathways in a pilot study using a plasmid repair reconstitution assay in lymphoblastoid and fibroblast cell lines from radiosensitive cancer patients and controls. Experiments using well-characterized mammalian DSB repair mutants demonstrated the ability of the assay to distinguish NHEJ sub-pathways. The proportion of direct end-joining repair compared with that of microhomology-directed repair was used as a functional end-point of DSB repair competence in the different cell lines. Results: We found that the overall level of NHEJ sub-pathway repair competency was similar in cell lines from radiosensitive patients and controls. Conclusion: These data suggest that this assay in these cell lineages has limited usefulness as a predictive screen for the endogenous DNA DSB repair competency of radiosensitive cancer patients' cells but can usefully characterize major cellular DSB repair phenotypes. © 2010 Blackwell Publishing Asia Pty Ltd. Source


Marcenaro M.,Divisions of Radiation Oncology | Vagge S.,Divisions of Radiation Oncology | Vagge S.,Italian National Cancer Institute | Belgioia L.,Divisions of Radiation Oncology | And 8 more authors.
Anticancer Research | Year: 2013

Aim: To evaluate the feasibility and outcomes of stereotactic body radiotherapy (SBRT) by helical tomotherapy (HT) for patients with primary or secondary lung cancer. Patients and Methods: Between March 2009 and January 2012, 56 patients were selected as candidates for the study and were divided into two subgroups. The ablative SBRT group included 27 patients with T1-T2 non-small cell lung cancer who received four to five largedose fractions in two weeks and the palliative SBRT group included 29 patients with lung metastases treated with eight lower-dose fractions in four weeks. Results: No differences in acute toxicities were found between different fractionation schemes with different overall treatment times. Actuarial local control at 24 months was better for the ablative group (69.6%) than for the palliative one (40.4%) (p=0.0019). Conclusion: HT-based SBRT was feasible and well-tolerated. Local control was satisfactory for patients treated with ablative SBRT but unsatisfactory for those treated with palliative SBRT. Outcomes also suggest the use of ablative SBRT fractionation for palliative intent. © 2013 Anticancer Research. Source

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