[Show abstract][Hide abstract] ABSTRACT: Aim of the study:
Sanazole and gemcitabine have been proven clinically as hypoxic cell radiosensitisers. This study was conducted to determine the radiation enhancing effects of sanazole and gemcitabine when administered together at relevant concentrations into hypoxic human MCF-7 and HeLa cells.
Material and methods:
A 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate the number of surviving cells. Cell cycle was determined by flow cytometry. Cell surviving fractions were determined by the standard in vitro colony formation assay.
The cell colony formation assay indicated that the radiosensitivity of hypoxic MCF-7 and HeLa cells was enhanced by sanazole or gemcitabine. The combination of the two drugs displayed significant radiation enhancing effects at the irradiation doses of 6, 8, and 10 Gy in both cell lines, which were arrested in the S phase.
This study indicated that the co-administration of the two drugs may result in a beneficial gain in radio-therapy for hypoxic breast cancer and cervical cancer.
[Show abstract][Hide abstract] ABSTRACT: This study presents quantitative and qualitative assessment of the image qualities in contrast-enhanced (CE) 3D-CT, 4D-CT and CE 4D-CT to identify feasibility for replacing the clinical standard simulation with a single CE 4D-CT for pancreatic adenocarcinoma (PDA) in radiotherapy simulation.
Ten PDA patients were enrolled and underwent three CT scans: a clinical standard pair of CE 3D-CT immediately followed by a 4D-CT, and a CE 4D-CT one week later. Physicians qualitatively evaluated the general image quality and regional vessel definitions and gave a score from 1 to 5. Next, physicians delineated the contours of the tumor (T) and the normal pancreatic parenchyma (P) on the three CTs (CE 3D-CT, 50% phase for 4D-CT and CE 4D-CT), then high density areas were automatically removed by thresholding at 500 HU and morphological operations. The pancreatic tumor contrast-to-noise ratio (CNR), signal-tonoise ratio (SNR) and conspicuity (C, absolute difference of mean enhancement levels in P and T) were computed to quantitatively assess image quality. The Wilcoxon rank sum test was used to compare these quantities.
In qualitative evaluations, CE 3D-CT and CE 4D-CT scored equivalently (4.4±0.4 and 4.3±0.4) and both were significantly better than 4D-CT (3.1±0.6). In quantitative evaluations, the C values were higher in CE 4D-CT (28±19 HU, p=0.19 and 0.17) than the clinical standard pair of CE 3D-CT and 4D-CT (17±12 and 16±17 HU, p=0.65). In CE 3D-CT and CE 4D-CT, mean CNR (1.8±1.4 and 1.8±1.7, p=0.94) and mean SNR (5.8±2.6 and 5.5±3.2, p=0.71) both were higher than 4D-CT (CNR: 1.1±1.3, p<0.3; SNR: 3.3±2.1, p<0.1). The absolute enhancement levels for T and P were higher in CE 4D-CT (87, 82 HU) than in CE 3D-CT (60, 56) and 4DCT (53, 70).
The individually optimized CE 4D-CT is feasible and achieved comparable image qualities to the clinical standard simulation. This study was supported in part by Philips Healthcare.
Medical Physics 06/2015; 42(6):3300. DOI:10.1118/1.4924239 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.
We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3-4N0-3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70-80 Gy), the lymph node-positive area (60-70 Gy), and the lymph node-negative area (50-60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan-Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis.
During the median follow-up of 3.9 years (range: 1-5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp; the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55; p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years.
Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.
[Show abstract][Hide abstract] ABSTRACT: Purpose: To study the feasibility of individually optimized contrastenhancement (CE) 4D-CT for pancreatic adenocarcinoma (PDA) in radiotherapy simulation. To evaluate the image quality and contrast enhancement of tumor in the CE 4D-CT, compared to the clinical standard of CE 3D-CT and 4D-CT.
Medical Physics 06/2014; 41(6):200-200. DOI:10.1118/1.4888240 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To quantitatively evaluate the inter-fractional variations in ITVs over the course of treatment using multiple 4DCTs and CBCTs for patients treated with SBRT for lung targets. To compare using ITV generated from all phases of a 4D or average intensity projection (ITV-AIP) as reference contours for image guidance.
Medical Physics 06/2014; 41(6):173-173. DOI:10.1118/1.4888129 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To improve the diagnostic quality of CT pulmonary angiography (CTPA) by individually optimizing a biphasic contrast injection function to achieve targeted uniform contrast enhancement. To compare the results against a previously reported discrete Fourier transform (DFT) approach.
This simulation study used the CTPA datasets of 27 consecutive patients with pulmonary thromboembolic disease (PE). An optimization approach was developed consisting of (1) computation of the impulse enhancement function (IEF) based on a test bolus scan, and (2) optimization of a biphasic contrast injection function using the IEF in order to achieve targeted uniform enhancement. The injection rates and durations of a biphasic contrast injection function are optimized by minimizing the difference between the resulting contrast enhancement curve and the targeted uniform enhancement curve, while conforming to the clinical constraints of injection rate and total contrast volume. The total contrast volume was limited first to the clinical standard of 65 ml, and then to the same amount used in the DFT approach for comparison. The optimization approach and the DFT approach were compared in terms of the root mean square error (RMSE) and total contrast volume used.
When the total contrast volume was limited to 65 ml, the optimization approach produced significantly better contrast enhancement (closer to the targeted uniform contrast enhancement) than the DFT approach (RMSE 17 HU vs 56 HU, p < 0.00001). On average, the optimization approach used 63 ml contrast, while the DFT approach used 50 ml with four patients exceeding 65 ml. When equivalent total contrast volume was used for individual patient, the optimization approach still generated significantly better contrast enhancement (RMSE 44 HU vs 56 HU, p < 0.01). Constraints for the injection function could be easily accommodated into the optimization process when searching for the optimal biphasic injection function.
The optimization approach generated individually optimized biphasic injection functions yielding significantly better contrast enhancement compared to the DFT approach. This new approach has the potential to improve the diagnostic quality of CTPA for PE.
Medical Physics 12/2013; 40(12):121906. DOI:10.1118/1.4829529 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To improve the diagnostic quality of CT angiography (CTPA) for pulmonary thromboembolic disease by individually optimizing a bi‐phasic contrast injection function to achieve uniform target contrast enhancement. To compare the results against a previously reported discrete Fourier transform (DFT) approach. Methods: This simulation study uses a retrospective dataset of 27 consecutive patients. We developed an optimization approach consists of two steps: 1. Compute the impulse enhancement function (IEF) based on the test bolus scan; 2. Optimize the contrast injection function using the IEF in order to achieve uniform target enhancement. We chose a bi‐phasic contrast injection function in which the injection rates and durations are optimized by minimizing the difference between its contrast enhancement curve and the uniform target enhancement curve. The contrast volume is limited either to the clinical standard of 65 mL or to the same amount used in the DFT approach. The optimization approach is compared against the DFT approaches in terms of the root mean square errors (RMSE) from the uniform target contrast enhancement curve and the contrast volume used. Results: When the contrast volume is limited to 65 mL, the optimization approach produces contrast enhancement significantly (p<.00001) closer to the uniform target contrast enhancement (mean RMSE 17 HU) than the DFT approach (mean RMSE 56 HU), for which the contrast volume is not even limited. When the contrast volume is limited to be the same amount used in the DFT approach, the optimization approach still generate significantly improved contrast enhancement than the DFT approach (RMSE 44 HU vs. 56 HU, p<.0099). Conclusion: The optimization approach generates individually optimized bi‐phasic injection functions yielding significantly improved contrast enhancement than the DFT approach. Its implementation in clinic has great potential to improve the diagnostic quality of CTPA. This work is supported in part by Philips Healthcare, Inc.
Medical Physics 06/2013; 40(6):483. DOI:10.1118/1.4815561 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To quantitatively evaluate the inter‐fractional variation in tumor volumes with repeated 4D‐CTs and repeated CBCTs for lung patients. To evaluate the uncertainties in patient set‐up that uses internal target volume (ITV) of 4D‐CT to match the soft tissue on CBCTs. Methods: We retrospectively selected 5 lung cancer patients: each with three 4D‐CTs (4D1, 4D2, and 4D3) and three CBCTs (C1, C2, and C3), and each CBCT was scanned within one week of a corresponding 4D‐CT. All CT images are registered to 4D1, together with contours on each image: ITV for 4D‐CT and gross tumor volumes (GTV) for CBCT. Then, these volumes are compared to ITV in 4D1 in terms of tumor volume, centroid distance, and volume overlap coefficient. Results: In each CBCT/4D‐CT pair, GTV in CBCT underestimate the ITV in 4D‐CT by 41.22±1.39 %. When normalized to the ITV volume in the 4D1, other ITVs of 4D‐CTs have an average volume of 1.07±0.13, and GTV in CBCTs have an average volume of 0.58±0.01. The centroid distance between ITV of 4D1 and a GTV of CBCT (5.6±11.9 mm) is larger than that between ITVs of 4D1and 4D2/4D3 (4.6±8.1 mm), while the CBCT GTV volumes are more included in the ITV of 4D1 (BinA: 0.863±0.018) than those of 4D2/4D3 (BinA: 0.735±0.033). From visual observation, the tumors presented in CBCTs are more similar to those in average projections compared to the ITVs of 4D‐CTs. Conclusions: The soft tissue alignment using 4D ITV on CBCT image has room for improvement. Although CBCT tumor seems more included, the centroid distance between CBCT‐GTV and 4D1‐ITV is larger than that between 4D2/4D3‐ITV and 4D1‐ITV. This, together with the underestimation of tumor volume from CBCT, makes current soft tissue alignment not as reliable as it seems. This work is supported in part by Philips Healthcare, Inc.
Medical Physics 06/2013; 40(6):151. DOI:10.1118/1.4814222 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: Contrast-enhanced (CE) 4D-CT has the advantage of both visualizing an abdominal tumor and estimating its motion in a single scan. Considering the large variation in the peak CE time from one patient to another, we propose to optimize the contrast injection delay time for individual patients so that the CE is maximized when scanning the tumor region in CE 4D-CT. Methods: We designed a flow phantom simulating the contrast enhancement and washing out in an organ. Peak CE time of a test injection (Tpeak.test) with 10 ml contrast was used to estimate the peak CE time of a full injection (Tpeak) with 140 ml contrast in the CE 4D-CT: Tpeak = Tpeak.test + (TID-TID.test), where TID.test and TID are the corresponding injection durations. We then computed an optimal contrast injection delay time, TIV = TO - Tpeak, where TO is the 4D-CT scan time from the starting position to the center of phantom. To verify that maximal CE is achieved with TIV, we performed five CE 4D-CT scans using an injection delay time of TIV + AT, where ΔT = +6, +3, 0, -3, and -6 s. The CE in a volume of interest at the center of the phantom was measured in each 4D-CT. Results: The phantom showed good reproducibility about ±1 s in the peak CE time of both test injection and full injection. The 4D-CT using the optimal TIV (ΔT = 0) showed the maximum contrast enhancement. The larger deviation from TIV, the lower was contrast enhancement. These results verified that the estimated optimal injection time delay achieved maximum contrast enhancement. Conclusions: It is feasible to estimate individually optimized injection delay time to maximally enhance a region or organ of interest in CE 4D-CT. This study is supported in part by Philips Healthcare. This study is supported in part by Philips Healthcare.
Medical Physics 06/2012; 39(6):3903. DOI:10.1118/1.4735932 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was to evaluate the influence of radiotherapy on the selenium serum levels of non-small cell cancer patients with brain metastases.
This prospective study included 95 non-small cell cancer patients with brain metastases treated by radiotherapy from December 2007 until November 2010. Plasma selenium levels were determined before and at the end of the radiotherapy. Age, body mass index (BMI), prior chemotherapy, pathological type and personal habits (smoking and alcoholism) were recorded for each patient.
The mean age was 63 years; the mean BMI was 27.6. Seventy-six patients (80%) were non-smokers. Sixty-two patients (65.3%) showed no drinking habits and 8 (8.4%) have no prior chemotherapy. Thirty-nine patients (41.1%) were adenocarcinoma, 51 (53.7%) were squamous cell carcinoma and five (5.3%) were large cell carcinoma. At the beginning of radiotherapy, the mean selenium level for all patients was 90.4 μg/l and after radiation this value dropped to 56.3 μg/l. Multivariate analysis showed statistically significant difference in the plasma selenium concentration before and after radiotherapy for age (P<0.001), BMI (P<0.001), smoking (P<0.001), alcoholism (P<0.001), prior chemotherapy (P<0.001) and pathological type (P<0.001).
Significant reduction in plasma levels of selenium was recorded in patients undergoing radiotherapy, suggesting attention to the nutritional status of this micronutrient and other antioxidant agents.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the effect of C-reactive protein (CRP) level on the prognosis of patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. Fifty-seven patients with locoregionally advanced laryngeal carcinoma (cT3-4, N0-3, M0) treated with chemoradiotherapy were reviewed retrospectively. Chemoradiotherapy comprised external beam radiotherapy to the larynx (70 Gy) with three cycles of cisplatin at 3-week intervals. Elevated CRP was defined as >8 mg/L. The survival rate was calculated using the Kaplan-Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model. During the median (range) follow-up of 5 years (1.3-5), 29 patients died from laryngeal cancer; the 5-year cancer-specific survival (CSS) rate was 49.12%. Fifteen patients had a high CRP level before chemoradiotherapy (>8 mg/L), and their CSS rate was significantly worse than that in the remaining patients (P = 0.003). Multivariate analysis showed that CRP and tumor site were independent prognostic indicators for CSS, with a hazard ratio of 2.66 (95% confidence interval (CI), 1.22-5.82; P = 0.014) and a hazard ratio of 1.67 (95% CI, 1.01-2.77; P = 0.045), respectively. Of those with elevated CRP, the CRP levels of ten patients became normal after chemoradiotherapy, of whom four were alive with no evidence of recurrence or metastasis during the follow-up. By contrast, all six with no CRP normalization after chemoradiotherapy died within 3.8 years. The elevation of CRP before treatment predicts a poor prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.