Survival after thermal ablation versus wedge resection for stage I non-small cell lung cancer < 1 cm and 1 to 2 cm: evidence from the US SEER database.

BACKGROUND: This study compared the survival outcomes after thermal ablation versus wedge resection in patients with stage I non-small cell lung cancer (NSCLC) ≤ 2 cm. METHODS: Data from the United States (US) National Cancer Institute Surveillance Epidemiology and End Results (SEER) database from 2004 to 2019 were retrospectively analyzed. Patients with stage I NSCLC and lesions ≤ 2 cm who received thermal ablation or wedge resection were included. Patients who received chemotherapy or radiotherapy were excluded. Propensity-score matching (PSM) was applied to balance the baseline characteristics between patients who underwent the two procedures. RESULTS: Univariate and Cox regression analyses were performed to determine the associations between study variables, overall survival (OS), and cancer-specific survival (CSS). After PSM, 328 patients remained for analysis. Multivariable Cox regression analysis revealed, compared to wedge resection, thermal ablation was significantly associated with a greater risk of poor OS (adjusted HR [aHR]: 1.34, 95% CI: 1.09-1.63, p = 0.004) but not CSS (aHR: 1.28, 95% CI: 0.96-1.71, p = 0.094). In stratified analyses, no significant differences were observed with respect to OS and CSS between the two procedures regardless of histology and grade. In patients with tumor size 1 to 2 cm, compared to wedge resection, thermal ablation was significantly associated with a higher risk of poor OS (aHR: 1.35, 95% CI: 1.10-1.66, p = 0.004). In contrast, no significant difference was found on OS and CSS between thermal ablation and wedge resection among those with tumor size < 1 cm. CONCLUSIONS: In patients with stage I NSCLC and tumor size < 1 cm, thermal ablation has similar OS and CSS with wedge resection.

2024 multidisciplinary consensus on image-guided lung tumor ablation from the Taiwan Academy of Tumor Ablation.

In this article, the multidisciplinary team of the Taiwan Academy of Tumor Ablation, who have expertise in treating lung cancer, present their perspectives on percutaneous image-guided thermal ablation (IGTA) of lung tumors. The modified Delphi technique was applied to reach a consensus on clinical practice guidelines concerning ablation procedures, including a comprehensive literature review, selection of panelists, creation of a rating form and survey, and arrangement of an in-person meeting where panelists agreed or disagreed on various points. The conclusion was a final rating and written summary of the agreement. The multidisciplinary expert team agreed on 10 recommendations for the use of IGTA in the lungs. These recommendations include terms and definitions, line of treatment planning, modality, facility rooms, patient anesthesia settings, indications, margin determination, post-ablation image surveillance, qualified centers, and complication ranges. In summary, IGTA is a safe and feasible approach for treating primary and metastatic lung tumors, with a relatively low complication rate. However, decisions regarding the ablation technique should consider each patient's specific tumor characteristics.

The safety and response of CT guided percutaneous cryoablation for lung nodules by 17-gauge needles.

BACKGROUND: The safety and efficacy of 17-gauge needles used in CT-guided percutaneous cryoablation for lung nodules were explored in this study. The purpose of the study was to compare the findings with earlier research and multi-center clinical trials that used various needle sizes. METHODS: Between 2016 and 2020, a retrospective study was conducted with approval from the institutional review board. A total of 41 patients were enrolled, and 71 lung nodules were treated in 63 cryoablation procedures using local anesthesia. Complication rates were recorded, and overall survival rates as well as tumor progression-free rates were calculated using the Kaplan-Meier method. RESULTS: Self-limited hemoptysis was caused by 12.9% of the procedures, and drainage was required for pneumothoraces resulting from 11.3% of them. The overall survival rates at one, two, three, and four years were 97%, 94%, 82%, and 67%, respectively. The tumor progression-free rates at one, two, three, and four years were 86.2%, 77%, 74%, and 65%, respectively. CONCLUSION: Cryoablation for lung nodules using 17-Gauge needles can achieve similar rates of survival and tumor control rates, similar or even lower complication rates as compared with other studies and multi-center trials using mixed sized needles.

Orlistat Resensitizes Sorafenib-Resistance in Hepatocellular Carcinoma Cells through Modulating Metabolism.

Sorafenib is one of the options for advanced hepatocellular carcinoma treatment and has been shown to extend median overall survival. However, sorafenib resistance often develops a few months after treatment. Hence, developing various strategies to overcome sorafenib resistance and understand the possible mechanisms is urgently needed. We first established sorafenib-resistant hepatocellular carcinoma (HCC) cells. Then, we found that sorafenib-resistant Huh7 cells (Huh7/SR) exhibit higher glucose uptakes and express elevated fatty acid synthesis and glucose metabolism-related proteins than their parental counterparts (Huh7). The current study investigated whether sorafenib resistance could be reversed by suppressing fatty acid synthesis, using a fatty acid synthase (FASN) inhibitor, orlistat, in HCC cells. FASN inhibition-caused changes in protein expressions and cell cycle distribution were analyzed by Western blot and flow cytometry, and changes in glucose uptakes were also evaluated by 18F-FDG uptake. Orlistat remarkably enhanced the cytotoxicity of sorafenib in both Huh7 and Huh7/SR cells, and flow cytometry showed that combination treatment significantly increased the sub-G1 population in both cell lines. Western blot revealed that the combination treatment effectively increased the ratio of Bax/Bcl-2 and decreased expressions of pERK; additionally, the combination treatment also strongly suppressed fatty acid synthesis-related proteins (e.g., FASN and SCD) in both cell lines. Lastly, the 18F-FDG uptake was repressed by the combination treatment in both cell lines. Our results indicated that orlistat-mediated FASN inhibition could overcome sorafenib resistance and enhance cell killing in HCC by changing cell metabolism.

A combination of sorafenib and radiotherapy reduces NF-κB activity and growth of hepatocellular carcinoma in an orthotopic mouse model.

Hepatocellular carcinoma (HCC) is difficult to diagnose at an early stage, and its prognosis is generally poor. Sorafenib is the primary treatment for unresectable advanced HCC and targets multiple receptor tyrosine kinases. However, sorafenib only extends the average survival time by 3 months. This observation indicates that sorafenib may need to be combined with other treatments to further improve outcomes. We previously showed that combination of sorafenib with radiotherapy (RT) enhances tumor inhibition in subcutaneous HCC mouse models compared with monotherapy. The present study demonstrated that combining sorafenib and RT could suppress tumor growth in an orthotopic HCC model by regulating apoptosis and NF-κB-related pathways. Moreover, decreased numbers of visible liver tumors and a smaller percentage of spleen metastases were found in the combination group. A transient drop in body weight was initially observed after RT, but progressive recovery of body weight occurred. The current study showed that the combination of sorafenib and RT could be a safe strategy for HCC treatment.

Fatty Acid Inhibition Sensitizes Androgen-Dependent and -Independent Prostate Cancer to Radiotherapy via FASN/NF-κB Pathway.

Elevated fatty acid synthase (FASN) has been reported in both androgen-dependent and -independent prostate cancers. Conventional treatment for prostate cancer is radiotherapy (RT); however, the following radiation-induced radioresistance often causes treatment failure. Upstream proteins of FASN such as Akt and NF-κB are found increased in the radioresistant prostate cancer cells. Nevertheless, whether inhibition of FASN could improve RT outcomes and reverse radiosensitivity of prostate cancer cells is still unknown. Here, we hypothesised that orlistat, a FASN inhibitor, could improve RT outcomes in prostate cancer. Orlistat treatment significantly reduced the S phase population in both androgen-dependent and -independent prostate cancer cells. Combination of orlistat and RT significantly decreased NF-κB activity and related downstream proteins in both prostate cancer cells. Combination effect of orlistat and RT was further investigated in both LNCaP and PC3 tumour-bearing mice. Combination treatment showed the best tumour inhibition compared to that of orlistat alone or RT alone. These results suggest that prostate cancer treated by conventional RT could be improved by orlistat via inhibition of FASN.

Synergistic effects of tetrandrine combined with ionizing radiation on a murine colorectal carcinoma­bearing mouse model.

Tetrandrine (TET), a traditional Chinese clinical agent, has been used for the treatment of many diseases, including cancers. The purpose of the present study was to investigate the combined effects of TET and ionizing radiation (IR) on murine CT26 colorectal adenocarcinoma cells in vitro and in vivo. A CT26 cell line transfected with dual HSV­1 thymidine kinase and firefly luciferase (luc) reporter genes was used. The half­maximal inhibitory concentration (IC50) of TET in CT26/tk­luc cells was ~10 µM. An additive effect was observed after combination of both agents based on a colony formation assay. Apoptosis and cleaved caspase­3 levels were increased significantly in cells after combination treatment, as shown by flow cytometric analysis, DNA fragmentation and western blotting. However, tumor growth inhibition and therapeutic efficacy of TET combined with IR in vivo were identified to be synergistic, as monitored by tumor growth delay time, measured with a digital caliper. A significant inhibition of tumor growth was identified in the combination group compared with the radiation only group. Furthermore, non­invasive bioluminescent imaging (BLI) and gamma scintigraphy were also used to evaluate therapeutic efficacy. Both modalities revealed that the best tumor growth control was under combination treatment among all groups. The present study demonstrated that TET is not only beneficial for chemotherapy, but also has potential as a radiosensitizer for the treatment of cancer.

Building a high-resolution T2-weighted MR-based probabilistic model of tumor occurrence in the prostate.

PURPOSE: We present a method for generating a T2 MR-based probabilistic model of tumor occurrence in the prostate to guide the selection of anatomical sites for targeted biopsies and serve as a diagnostic tool to aid radiological evaluation of prostate cancer. MATERIALS AND METHODS: In our study, the prostate and any radiological findings within were segmented retrospectively on 3D T2-weighted MR images of 266 subjects who underwent radical prostatectomy. Subsequent histopathological analysis determined both the ground truth and the Gleason grade of the tumors. A randomly chosen subset of 19 subjects was used to generate a multi-subject-derived prostate template. Subsequently, a cascading registration algorithm involving both affine and non-rigid B-spline transforms was used to register the prostate of every subject to the template. Corresponding transformation of radiological findings yielded a population-based probabilistic model of tumor occurrence. The quality of our probabilistic model building approach was statistically evaluated by measuring the proportion of correct placements of tumors in the prostate template, i.e., the number of tumors that maintained their anatomical location within the prostate after their transformation into the prostate template space. RESULTS: Probabilistic model built with tumors deemed clinically significant demonstrated a heterogeneous distribution of tumors, with higher likelihood of tumor occurrence at the mid-gland anterior transition zone and the base-to-mid-gland posterior peripheral zones. Of 250 MR lesions analyzed, 248 maintained their original anatomical location with respect to the prostate zones after transformation to the prostate. CONCLUSION: We present a robust method for generating a probabilistic model of tumor occurrence in the prostate that could aid clinical decision making, such as selection of anatomical sites for MR-guided prostate biopsies.

Investigation of an optimized scanning protocol for the dentomaxillofacial region using 320-slice multidetector computed tomography.

OBJECTIVES: To propose an imaging protocol that provides satisfactory image quality for oral examination while minimizing radiation dosage using 320-slice multidetector CT (MDCT). METHODS: An anthropomorphic head phantom was scanned using 320 MDCT with protocols combining different scanning modes: volume scanning (whole or local) vs helical scanning (80- or 64-slice detectors); tube voltage settings (80 kVp, 120 kVp and 135 kVp); and tube current settings (60 mA, 80 mA, 100 mA and 120 mA). A total of six anatomical bone structures and three anatomical soft-tissue structures were assessed using quantitative and qualitative analysis in the three orthographic planes (axial, sagittal and coronal). A figure of merit (FOM) was used to determine the optimal imaging protocol in terms of tube voltage, tube current and scanning mode. RESULTS: The 80-kVp setting had the worst quantitative and qualitative results (both p < 0.001) compared with the 135-kVp and 120-kVp settings, especially for soft-tissue structures. A significant difference was noted for the scores obtained using a tube current between 120 mA and 60 mA by quantitative analysis, but not by qualitative analysis. Volume scans using either whole or local modes had a significantly higher FOM than helical scanning of 80 or 64 slices. CONCLUSIONS: In 320 MDCT, a protocol using 135 kVp, 80 mA and the volume-scanning mode (whole or local) offers adequate visualization of both soft-tissue and bone structures while keeping the radiation dose as low as possible. This may therefore be considered a first choice among a wide selection of scanning protocols for dentomaxillofacial CT.

Reducing Artifacts during Arterial Phase of Gadoxetate Disodium-enhanced MR Imaging: Dilution Method versus Reduced Injection Rate.

Purpose To compare two contrast material-administration protocols (dilution vs slow injection) in terms of their effectiveness in arterial phase artifact reduction at gadoxetic acid-enhanced magnetic resonance (MR) imaging. Materials and Methods This HIPAA-compliant retrospective case-controlled cohort study was approved by the institutional review board, with a waiver of informed patient consent. A total of 318 consecutive patients undergoing gadoxetic acid-enhanced MR imaging were placed into one of two subcohorts of 159 consecutive patients each: the dilution subcohort (gadoxetic acid was diluted 1:1 with saline and injected at a rate of 2.0 mL/sec) and the slow injection subcohort (gadoxetic acid was not diluted and was injected at a rate of 1.0 mL/sec). Eighty-nine patients in the dilution subcohort also underwent follow-up MR imaging with the slow injection method, and 34 patients in the slow injection subcohort underwent follow-up MR imaging with the dilution method. Both patient- and image-based analyses, as well as intraindividual analysis, were used to compare two parameters-mean artifact score rated by two observers using a five-point scale and frequency of severe artifact-between the dilution and slow injection subcohorts with the Wilcoxon Mann-Whitney test, χ2 test, and generalized estimating equation. Results In both patient- and image-based analyses, the mean artifact score and frequency of severe artifact were lower in the dilution subcohort (mean, 1.46% and 3.8% [six of 159]) than in the slow injection subcohort (mean, 1.95% and 15.1% [24 of 159]) (P ≤ .001 and P < .001, respectively). In intraindividual analysis, both variables were also decreased in the dilution subcohort (P = .007 and P = .001, respectively). We found the two variables to be significantly increased in the slow injection subcohort when compared with that in the dilution subcohort for three different MR platforms (P < .05). Conclusion In comparison with slow injection of undiluted contrast material at a rate of 1.0 mL/sec, gadoxetic acid diluted to 50% and injected at a rate of 2 mL/sec had a significantly less severe ghosting artifact in the arterial phase of gadoxetic acid-enhanced MR imaging. © RSNA, 2016 Online supplemental material is available for this article.

In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2-based Diagnostic Performance for Detection of Prostate Cancer.

Purpose To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging-guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. Materials and Methods This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2. Results Prostate cancer was detected in 63 of 106 patients (59.4%) and in 72 of 134 targets (53.7%) with 3-T MR imaging. Forty-nine of 72 targets (68.0%) had clinically significant cancer (Gleason score ≥ 7). One complication occurred (urosepsis, 0.9%). Patients who had positive target findings had lower apparent diffusion coefficient values (875 × 10-6 mm2/sec vs 1111 × 10-6 mm2/sec, respectively; P < .01), smaller prostate volume (47.2 cm3 vs 75.4 cm3, respectively; P < .01), higher PSA density (0.16 vs 0.10, respectively; P < .01), and higher proportion of PI-RADS version 2 category 3-5 scores when compared with patients with negative target findings. MR targets with PI-RADS version 2 category 2, 3, 4, and 5 scores had a positive diagnostic yield of three of 23 (13.0%), six of 31 (19.4%), 39 of 50 (78.0%), and 24 of 29 (82.8%) targets, respectively. No differences were detected in areas under the curve for PI-RADS version 2 versus 1. Conclusion In-bore 3-T MR-guided biopsy is safe and effective for prostate cancer diagnosis when stratified according to PI-RADS versions 1 and 2. ©RSNA, 2016.

Preliminary Outcome of Microwave Ablation of Hepatocellular Carcinoma: Breaking the 3-cm Barrier?

PURPOSE: To evaluate preliminary outcomes after microwave ablation (MWA) of hepatocellular carcinoma (HCC) up to 5 cm and to determine the influence of tumor size. MATERIALS AND METHODS: Electronic records were searched for HCC and MWA. Between January 2011 and September 2014, 173 HCCs up to 5 cm were treated by MWA in 129 consecutive patients (89 men, 40 women; mean age, 66.9 y ± 9.5). Tumor characteristics related to local tumor progression and primary and secondary treatment efficacy were evaluated by univariate analysis. Outcomes were compared between tumors ≤ 3 cm and tumors > 3 cm. RESULTS: Technical success, primary efficacy, and secondary efficacy were 96.5%, 99.4%, and 94.2% at a mean follow-up period of 11.8 months ± 9.8 (range, 0.8-40.6 mo). Analysis of tumor characteristics showed no significant risk factor for local tumor progression, including subcapsular location (P = .176), tumor size (P = .402), and perivascular tumor location (P = .323). The 1-year and 2-year secondary or overall treatment efficacy rates for tumors measuring ≤ 3 cm were 91.2% and 82.1% and for tumors 3.1-5 cm were 92.3% and 83.9% (P = .773). The number of sessions to achieve secondary efficacy was higher in the larger tumor group (1.13 vs 1.06, P = .005). There were three major complications in 134 procedures (2.2%). CONCLUSIONS: With use of current-generation MWA devices, percutaneous ablation of HCCs up to 5 cm can be achieved with high efficacy.

Prediction of microvascular invasion of hepatocellular carcinoma: preoperative CT and histopathologic correlation.

OBJECTIVE: The objective of our study was to prospectively investigate whether nonsmooth margins detected on multiphasic CT images correlate with the presence and location of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: A total of 102 patients with preoperative CT findings of solitary HCC were prospectively enrolled. Tumor size, tumor capsule, tumor margins, and peritumoral enhancement on preoperative CT images were assessed. Histopathologic results including the following were also recorded: tumor differentiation; liver fibrosis score; presence or absence of MVI; and, if present, the location of MVI. Correlation between tumor margin on preoperative CT images and histopathologic location of MVI was determined. RESULTS: Pathologic examination revealed MVI in 60 of the 102 HCC specimens. Although the results of the univariate analysis showed that tumor size, higher Edmondson-Steiner grade, and nonsmooth tumor margins were associated with MVI, multivariate analysis revealed that only nonsmooth margins correlated with the presence of MVI in HCC (p < 0.001). Of the 60 HCC specimens with histopathologic evidence of MVI, 40 exhibited focal nonsmooth margins. In addition, the locations of the nonsmooth margins and MVI were similar in 36 of the 40 specimens. CONCLUSION: Nonsmooth tumor margins correlated with the histopathologic presence and location of MVI. Therefore, nonsmooth margins detected on multiphasic CT may be predictive of MVI in HCC.

Using [¹8F]FBAU for imaging brain tumor progression in an F98/tk-luc glioma-bearing rat model.

1-(2-Deoxy-2-[18F]fluoro-ß-D-arabinofuranosyl)-5-bromouracil ([18F]FBAU), a substitute for thymine, has been reported as an effective reporter probe by which to trace cellular metabolism with its positron emission. In the present study, a rat xenograft model bearing F98 glioma transfected with dual reporter genes, herpes simplex virus type 1 thymidine kinase (HSV1-tk) and firefly luciferase (luc) was used for monitoring tumor progression by multimodalities of molecular imaging using [18F]FBAU and D-luciferase as probes. Rat F98 glioma cells were transfected with the pC1-tk-IRES-luc vectors. The selected stable clone was renamed as the F98/tk-luc cell line. Fischer 344 male rats bearing orthotropic F98/tk-luc gliomas in the left brain were used. On day 13 post tumor inoculation, biodistribution, positron emission tomography (PET), magnetic resonance imaging (MRI) and ex vivo autoradiography were performed. The surviving fraction of F98/tk-luc cells treated with 15 µM ganciclovir (GCV) was 15.9%, and the uptake of [131I]FIAU in these cells was significantly enhanced when compared with F98 cells. The correlation coefficient of tumor volume vs. the bioluminescence in the F98/tk-luc glioma-bearing rats was 0.90. The biodistribution showed that the accumulation ratios of [18F]FBAU for glioma-to-normal brain were 9.16, 14.24, 5.7 and 13.7 at 30, 60, 90 and 120 min post i.v. injection, respectively. Consistent tumor enhancement of [18F]FBAU/PET imaging was also noted from 30-90 min post injection. Ex vivo autoradiography also confirmed significant [18F]FBAU uptake in tumors. In conclusion, [18F]FBAU may be used as a PET probe for monitoring glioma progression in animal models and may have potential for clinical use as well.

Primary lung cancers <1 cm found with MR screening appeared larger with half-Fourier sequences than with three-dimensional acquisition techniques.

PURPOSE: The purpose was to objectively evaluate image quality characteristics of half-Fourier single-shot turbo spin-echo (HASTE) and three-dimensional volumetric interpolated breath-hold examination (3D-VIBE) for small (<1 cm) lung cancers found by magnetic resonance imaging (MRI) screening. METHODS: From 2000 to 2009, 19,000 normal subjects were screened by MRI, and 15 cases were found to have lung cancers <1 cm. Those nodules were analyzed by image quality indices such as the signal to noise ratio, signal difference to noise ratio, percent contrast, percent contrast to noise ratio, and signal ratio of tumor to normal lung parenchyma. The area of the tumors measured by the two MR sequences and the computed tomography (CT) was compared. RESULTS: The lung cancers showed significantly higher percent contrast, percent contrast to noise, and the signal ratio of tumor to normal lung parenchyma by 3D-VIBE as compared to HASTE. Tumor area estimated by HASTE was significantly larger than that estimated by VIBE. There was no significant difference in the signal to noise ratio and signal difference to noise ratio between the two MR sequences. CONCLUSIONS: The 3D acquisition technique offers high contrast and contrast to noise ratios, while HASTE is associated with closer approximation of area estimation as compared to CT. Both sequences have similar signal to noise ratios and signal difference to noise ratios. The HASTE sequence is considered to be an essential part of imaging protocol in MR screening of lung especially for small nodules.

Breast cancers detected by breast MRI screening and ultrasound in asymptomatic Asian women: 8 years of experience in Taiwan.

BACKGROUND: This study investigated one-stop breast screening combining magnetic resonance imaging (MRI) and ultrasound (US) in asymptomatic Asian women. METHODS: 3,586 asymptomatic women (mean age, 45.3 years) were retrospectively analyzed by breast MRI followed by US. US-guided biopsy was performed when the MRI-detected lesion was confirmed by US. When the lesion was not detected on the initial US, a second-look US guided by MRI findings was performed. Then biopsy was done. MRI-positive and US-negative patients were followed up according to MRI lesion size, MRI lesion morphology, and mammographic diagnosis. RESULTS: In total, 115 subjects had suspicious malignant lesions and received US-guided biopsy, and 47 malignant lesions, including 35 invasive cancers and 12 carcinoma in situ (CIS) lesions, were diagnosed. More than half (22/35, 63%) of the women with invasive cancer were <50 years of age, and 27 (57.4%) of the 47 cancer cases had early breast cancers. Two invasive cancers (5.7%) and 7 CIS lesions (58.3%) were found at the second-look US. The overall cancer incidence was 1.31% (47/3,586) and increased to 2.2% (78/3,586) if precancerous lesions were included. Subjects aged 41-50 years had the highest incidence of cancer detection (1.97%). Five MRI and US-negative cases had cancers found 1 year after the screening. CONCLUSIONS: The results from the one-stop breast screening in this study showed that combining MRI and US is an efficient multimodality tool for screening asymptomatic Asian women in a metropolitan area of Taiwan who had concerns about the diagnosis and radiation of mammography.

Sorafenib sensitizes human colorectal carcinoma to radiation via suppression of NF-κB expression in vitro and in vivo.

Over-expression of transcription factor nuclear factor-κB (NF-κB) in the residual tumor after the treatment is often observed at the later period of cancer radiotherapy, results in tumor radioresistance and poor treatment outcome. In this study, we combined sorafenib, a multikinase inhibitor, with ionizing radiation to evaluate the therapeutic effect, and to elucidate the possible mechanism responsible for the radiosensitization of sorafenib on a human HT29/tk-luc colorectal carcinoma in vitro and in vivo. Clonogenic survival and cell cycle analysis were used to evaluate the cytotoxicity of sorafenib in vitro. The combination effect and the role of NF-κB in therapeutic efficacy with respects in apoptosis and tumor cell invasion were studied with HT29/tk-luc tumor-bearing animal model. The expression of NF-κB and its downstream-related proteins were assayed with electrophoretic mobility shift assay (EMSA) and Western blot. Sorafenib combined with radiation shows the synergistic cytotoxicity on HT29/tk-luc cells and increased tumor cell apoptosis. Both EMSA and Western blot show that the NF-κB activity induced by radiation is significantly suppressed by sorafenib. Combination of sorafenib and radiation shows the maximum tumor growth inhibition as compared to that of sorafenib alone or radiation alone in vivo (P<0.001). In conclusion, the effect of sorafenib combined with radiation for the treatment of human colorectal carcinoma is synergistic. The mechanism of synergism is through the inhibition of radiation-induced NF-κB expression and its regulated downstream gene products.

Magnetic resonance imaging for lung cancer detection: experience in a population of more than 10,000 healthy individuals.

BACKGROUND: Recent refinements of lung MRI techniques have reduced the examination time and improved diagnostic sensitivity and specificity. We conducted a study to assess the feasibility of MRI for the detection of primary lung cancer in asymptomatic individuals. METHODS: A retrospective chart review was performed on images of lung parenchyma, which were extracted from whole-body MRI examinations between October 2000 and December 2007. 11,766 consecutive healthy individuals (mean age, 50.4 years; 56.8% male) were scanned using one of two 1.5-T scanners (Sonata and Sonata Maestro, Siemens Medical Solutions, Erlangen, Germany). The standard protocol included a quick whole-lung survey with T2-weighted 2-dimensional half Fourier acquisition single shot turbo spin echo (HASTE) and 3-dimensional volumetric interpolated breath-hold examination (VIBE). Total examination time was less than 10 minutes, and scanning time was only 5 minutes. Prompt referrals and follow-ups were arranged in cases of suspicious lung nodules. RESULTS: A total of 559 individuals (4.8%) had suspicious lung nodules. A total of 49 primary lung cancers were diagnosed in 46 individuals: 41 prevalence cancers and 8 incidence cancers. The overall detection rate of primary lung cancers was 0.4%. For smokers aged 51 to 70 years, the detection rate was 1.4%. TNM stage I disease accounted for 37 (75.5%). The mean size of detected lung cancers was 1.98 cm (median, 1.5 cm; range, 0.5-8.2 cm). The most histological types were adenocarcinoma in 38 (77.6%). CONCLUSION: Rapid zero-dose MRI can be used for lung cancer detection in a healthy population.

Volumetric intensity-modulated Arc (RapidArc) therapy for primary hepatocellular carcinoma: comparison with intensity-modulated radiotherapy and 3-D conformal radiotherapy.

BACKGROUND: To compare the RapidArc plan for primary hepatocellular carcinoma (HCC) with 3-D conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans using dosimetric analysis. METHODS: Nine patients with unresectable HCC were enrolled in this study. Dosimetric values for RapidArc, IMRT, and 3DCRT were calculated for total doses of 45~50.4 Gy using 1.8 Gy/day. The parameters included the conformal index (CI), homogeneity index (HI), and hot spot (V107%) for the planned target volume (PTV) as well as the monitor units (MUs) for plan efficiency, the mean dose (Dmean) for the organs at risk (OAR) and the maximal dose at 1% volume (D1%) for the spinal cord. The percentage of the normal liver volume receiving ≥ 40, > 30, > 20, and > 10 Gy (V40 Gy, V30 Gy, V20 Gy, and V10 Gy) and the normal tissue complication probability (NTCP) were also evaluated to determine liver toxicity. RESULTS: All three methods achieved comparable homogeneity for the PTV. RapidArc achieved significantly better CI and V107% values than IMRT or 3DCRT (p < 0.05). The MUs were significantly lower for RapidArc (323.8 ± 60.7) and 3DCRT (322.3 ± 28.6) than for IMRT (1165.4 ± 170.7) (p < 0.001). IMRT achieved a significantly lower Dmean of the normal liver than did 3DCRT or RapidArc (p = 0.001). 3DCRT had higher V40Gy and V30 Gy values for the normal liver than did RapidArc or IMRT. Although the V10 Gy to the normal liver was higher with RapidArc (75.8 ± 13.1%) than with 3DCRT or IMRT (60.5 ± 10.2% and 57.2 ± 10.0%, respectively; p < 0.01), the NTCP did not differ significantly between RapidArc (4.38 ± 2.69) and IMRT (3.98 ± 3.00) and both were better than 3DCRT (7.57 ± 4.36) (p = 0.02). CONCLUSIONS: RapidArc provided favorable tumor coverage compared with IMRT or 3DCRT, but RapidArc is not superior to IMRT in terms of liver protection. Further studies are needed to establish treatment outcome differences between the three approaches.

Detection of intracranial hemorrhage: comparison between gradient-echo images and b0 images obtained from diffusion-weighted echo-planar sequences on 3.0T MRI.

In this study, we compared the effectiveness of b0 echo-planar MR images (EPI) imaging with gradient recalled echo (GRE) in detecting acute hemorrhage. Brain images in 69 patients who suffered from acute infarction were reviewed. Nine of them had suffered from acute hemorrhage. Comparing b0EPI and GRE images side-by-side, we found no significant different effectiveness in detecting hemorrhage (P = .522, > or =.05). We concluded that b0EPI imaging could detect hemorrhagic lesions as effectively as GRE can without additional acquisition time.