[en] Purpose: To quantify interobserver variation in gross tumor volume (GTV) localization using CT images for patients with non-small-cell lung carcinoma and poorly defined tumors on CT and to determine whether variability would be reduced if coregistered 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG)-hybrid positron emission tomography (PET) with CT images were used. Methods and Materials: Prospectively, 30 patients with non-small-cell lung carcinoma had CT and FDG-hybrid PET examinations in radiation treatment position on the same day. Images were coregistered using eight fiducial markers. Guidelines were established for contouring GTVs. Three radiation oncologists performed localization independently. The coefficient of variation was used to assess interobserver variability. Results: The size of the GTV defined showed great variation among observers. The mean ratios of largest to smallest GTV were 2.31 and 1.56 for CT only and for CT/FDG coregistered data, respectively. The addition of PET reduced this ratio in 23 of 30 cases and increased it in 7. The mean coefficient of variation for GTV based on the combined modalities was significantly smaller (p<0.01) than that for CT data only. Conclusions: High observer variability in CT-based definition of the GTV can occur. A more consistent definition of the GTV can often be obtained if coregistered FDG-hybrid PET images are used

[en] Purpose: To prospectively study the impact of coregistering ¹⁸F-fluoro-deoxy-2-glucose hybrid positron emission tomographic (FDG-PET) images with CT images on the planning target volume (PTV), target coverage, and critical organ dose in radiation therapy planning of non-small-cell lung carcinoma. Methods and Materials: Thirty patients with poorly defined tumors on CT, referred for radical radiation therapy, underwent both FDG-PET and CT simulation procedures on the same day, in radiation treatment position. Image sets were coregistered using external fiducial markers. Three radiation oncologists independently defined the gross tumor volumes, using first CT data alone and then coregistered CT and FDG-PET data. Standard margins were applied to each gross tumor volume to generate a PTV, and standardized treatment plans were designed and calculated for each PTV. Dose-volume histograms were used to evaluate the relative effect of FDG information on target coverage and on normal tissue dose. Results: In 7 of 30 (23%) cases, FDG-PET information changed management strategy from radical to palliative. In 5 of the remaining 23 (22%) cases, new FDG-avid nodes were found within 5 cm of the primary tumor and were included in the PTV. The PTV defined using coregistered CT and FDG-PET would have been poorly covered by the CT-based treatment plan in 17-29% of cases, depending on the physician, implying a geographic miss had only CT information been available. The effect of FDG-PET on target definition varied with the physician, leading to a reduction in PTV in 24-70% of cases and an increase in 30-76% of cases. The relative change in PTV ranged from 0.40 to 1.86. On average, FDG-PET information led to a reduction in spinal cord dose but not in total lung dose, although large differences in dose to the lung were seen for a few individuals. Conclusion: The coregistration of planning CT and FDG-PET images made significant alterations to patient management and to the PTV. Ultimately, changes to the PTV resulted in changes to the radiation treatment plans for the majority of cases. Where possible, we would recommend that FDG-PET data be integrated into treatment planning of non-small-cell lung carcinoma, particularly for three-dimensional conformal techniques

[en] Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT

[en] Introduction: Our aim was to conduct a Phase I clinical trial to determine the feasibility of intraoperative detection of tumor margins in HER2 positive breast carcinoma using a hand-held γ-probe following administration of ¹¹¹In-DTPA-trastuzumab Fab fragments. Accurate delineation of tumor margins is important for preventing local recurrence. Methods: Six patients with HER2-positive in situ or invasive ductal carcinoma were administered 74 MBq (0.5 mg) of ¹¹¹In-DTPA-trastuzumab Fab fragments and counts in the tumor, surgical cavity wall and en face margins were measured intraoperatively at 72 h post-injection using the Navigator or C-Trak γ-probes. Margins were evaluated histologically. Quantitative whole body planar imaging was performed to estimate radiation absorbed doses using OLINDA/EXM software. SPECT imaging of the thorax was performed to evaluate tumor uptake. The pharmacokinetics of elimination from the blood and plasma were determined over 72 h. Results: There were no acute adverse reactions from ¹¹¹In-DTPA-trastuzumab Fab fragments and no changes in hematological or biochemical indices were found over a 3 month period. ¹¹¹In-DTPA-trastuzumab Fab fragments exhibited a biphasic elimination from the blood and plasma with t_1/2α = 11.9 h and 7.5 h, respectively, and t_1/2β = 26.6 and 20.7 h, respectively. The radiopharmaceutical accumulated in the liver, spleen and kidneys. SPECT imaging did not reveal tumor in any patient. The mean effective dose was 0.146 mSv/MBq (10.8 mSv for 74 MBq). Counts in excised tumors were low but were higher than in margins. Margins in two patients harboured tumor but this was not correlated with counts obtained using the γ-probes. Surgical cavity counts were high and likely due to detection of γ-photons outside the surgical field. Conclusion: We conclude that it was not feasible, at least at the administered amount of radioactivity used in this study, to reliably detect the margins of disease in patients with in situ or invasive ductal carcinoma intraoperatively using a hand-held γ-probe and ¹¹¹In-DTPA-trastuzumab Fab fragments due to low uptake in the tumor and involved margins