Biostatistics and Clinical Trials

Genova, Italy

Biostatistics and Clinical Trials

Genova, Italy

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Tucker J.D.,Wayne State University | Vadapalli M.,Wayne State University | Joiner M.C.,Wayne State University | Ceppi M.,Biostatistics and Clinical Trials | And 2 more authors.
Radiation Research | Year: 2013

The frequency of binucleated cells containing one or more micronuclei (MNBN cells) in cytokinesis-blocked peripheral blood lymphocytes can be used to determine whether a person has received an overexposure to ionizing radiation. However, the absence of a pre-exposure sample can preclude precise dosimetry. Here we use a database of MNBN cell frequencies in peripheral blood lymphocytes from 3,104 apparently healthy, unexposed, control subjects aged birth to 88 years, contributed by laboratories participating in the HUMN project. To determine whether a putatively exposed person has actually received a measurable dose, that person's peripheral blood lymphocyte MNBN frequency is compared to values from age and gender-matched controls in the database. If the subject's frequency is significantly higher than the controls, then a cobalt-60 dose-response curve obtained with the cytokinesis-block micronucleus (CBMN) assay in human peripheral blood lymphocytes is used to estimate the minimum dose of low-LET radiation that could have caused the increase. The response curve was generated with 11 acutely administered doses ranging from 0-4 Gy; the majority of doses were in the low end of this range to provide an accurate estimate of the linear portion of the response. The minimum detectable acute whole-body dose at the 95% prediction level and their corresponding 95% confidence intervals are 0.18 Gy (0.15-0.22) and 0.20 (0.17-0.24) Gy for 20-year-old males and females, respectively. Corresponding values for 50 year olds are 0.23 Gy (0.19-0.26) and 0.25 (0.21-0.29) Gy, and for 70 year olds are 0.24 (0.21-0.28) Gy and 0.26 (0.22-0.31) Gy. The minimum detectable chronic doses are approximately fivefold higher for both genders. These types of analyses, including knowledge of assay variability, will improve our understanding of the requirements and limitations for biodosimetry when a pre-exposure micronucleus value is unavailable and reliance on historical baseline micronucleus values is required. © 2013 by Radiation Research Society.


Gronchi A.,Fondazione IRCCS Instituto Nazionale Dei Tumori | De Paoli A.,Centro Of Riferimento Oncologico | Dani C.,Biostatistics and Clinical Trials | Merlo D.F.,Biostatistics and Clinical Trials | And 14 more authors.
European Journal of Cancer | Year: 2014

Background To study feasibility, safety and activity of the combination of high-dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative treatment for resectable localised retroperitoneal sarcoma (RPS). Methods Patients received three cycles of HLI (14 g/m2). RT was started in combination with second cycle and administered up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. Primary end-point was 3-year relapse free survival (RFS). The trial is registered with ITASARC-â̂ - II-2004-003. Findings Between December 2003 and 2010, 83 patients were recruited. Main histological subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated liposarcoma (26/83, 31%), leiomyosarcoma (14/83, 17%). Median tumour size was 120 mm (interquartile (IQ) range = 82-160). The overall preoperative treatment was completed in 60 patients. Chemotherapy (CT) was completed in 65, while RT in 73. Four patients progressed before surgery and were not operated. 79 patients underwent surgery. At a median follow-up of 4.8 years (IQ range = 3-6.1), 23 and 15 patients developed local recurrence (LR) and distant metastases (DM); 30 patients died of disease. 3 and 5-year RFS and overall survival were 0.56 (90% confidence interval (CI): 0.45, 0.65) and 0.44 (90% CI: 0.27, 0.48), and 0.74 (90% CI: 0.62, 0.81) and 0.59 (90% CI: 0.33, 0.58). Crude cumulative incidence of LR and DM at 5 years were 0.37 (standard error (SE): 0.06) and 0.26 (SE: 0.06). Interpretation The combination of preoperative HLI and RT was feasible in two thirds of patients, while preoperative RT could be completed in most (73/83). Although a systemic coverage can be added to RT when this is felt to be appropriate, the ongoing international phase III trial is exploring the role of RT alone. Funding This is a pure academic trial. No funding sources contributed to it. © 2013 Elsevier Ltd. All rights reserved.


PubMed | Treviso General Hospital, Institute for Cancer Research and Treatment at Candiolo, Centro Of Riferimento Oncologico, Biostatistics and Clinical Trials and 2 more.
Type: Clinical Trial, Phase I | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2014

To study feasibility, safety and activity of the combination of high-dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative treatment for resectable localised retroperitoneal sarcoma (RPS).Patients received three cycles of HLI (14 g/m2). RT was started in combination with second cycle and administered up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. Primary end-point was 3-year relapse free survival (RFS). The trial is registered with ITASARC_II_2004_003.Between December 2003 and 2010, 83 patients were recruited. Main histological subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated liposarcoma (26/83, 31%), leiomyosarcoma (14/83, 17%). Median tumour size was 120 mm (interquartile (IQ) range=82-160). The overall preoperative treatment was completed in 60 patients. Chemotherapy (CT) was completed in 65, while RT in 73. Four patients progressed before surgery and were not operated. 79 patients underwent surgery. At a median follow-up of 4.8 years (IQ range = 3-6.1), 23 and 15 patients developed local recurrence (LR) and distant metastases (DM); 30 patients died of disease. 3 and 5-year RFS and overall survival were 0.56 (90% confidence interval (CI): 0.45, 0.65) and 0.44 (90% CI: 0.27, 0.48), and 0.74 (90% CI: 0.62, 0.81) and 0.59 (90% CI: 0.33, 0.58). Crude cumulative incidence of LR and DM at 5 years were 0.37 (standard error (SE): 0.06) and 0.26 (SE: 0.06).The combination of preoperative HLI and RT was feasible in two thirds of patients, while preoperative RT could be completed in most (73/83). Although a systemic coverage can be added to RT when this is felt to be appropriate, the ongoing international phase III trial is exploring the role of RT alone.This is a pure academic trial. No funding sources contributed to it.

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