Technology in Cancer Research and Treatment

The use of external surrogates to predict tumor motion in real-time for extra-cranial sites requires the use of accurate correlation models. This is extremely challenging when motion prediction is to be performed over several breathing cycles, as occurs for realtime tumor tracking with Cyberknife® Synchrony®. In this work we compare three different approaches to infer tumor motion based on external surrogates, since no comparative study is available to assess the accuracy of correlation models in tumor tracking over a long time period. We selected 20 cases in a database of 130 patients treated with realtime tumor tracking by means of the Synchrony® module. The implemented correlation models comprise linear/quadratic correlation, artificial neural networks and fuzzy logic. The accuracy of each correlation model is evaluated on the basis of ground truth tumor position information acquired during treatment, as detected by means of stereoscopic X-ray imaging. Results show that the implemented models achieve an error reduction with respect to Synchrony®, measured at the 95% confidence level, up to 10.8% for the fuzzy logic approach. This latter is able to partly reduce the incidence of tumor tracking errors above 6 mm, resulting in improved accuracy for larger discrepancies. In conclusion, complex models are suggested to predict tumor motion over long time periods. This leads to an effective improvement with respect to Cyberknife® Synchrony®. Future studies will investigate the sensitivity of the implemented models to the input database, in order to define optimal strategies.

Stereotactic body radiotherapy (SBRT) is a new treatment modality for prostate cancer. The current study evaluates CyberKnife® SBRT and reports toxicity and early Prostate-Specific Antigen (PSA) kinetics. From June 2006 to August 2009, 45 low-and intermediate-risk prostate cancer patients received Cyberknife SBRT of 35 Gy in five fractions with 95% minimum target coverage. Median follow-up was 20-months (range 6–42-months). Seventeen patients received androgen-deprivation therapy also. Acute complications were mild, short-lived and no greater than Grade 2 by RTOG scale. Late toxicities consisted of one patient (2.2%) experiencing Grade 2 rectal, one patient (2.2%) Grade 3 and four patients (8.8%) with Grade 1 urinary toxicity. PSA in all patients progressively declined from a mean 4.7 ng/ml baseline to 1.48 ng/ml at three months, to 0.68 ng/ml at 12 months and to 0, 35 ng/ml at 24 months. The 28 hormon-naive patients had the mean PSA value of 1.1 ng/ml at one year from a mean 6.65 ng/ml baseline. There was a significant PSA value reduction in 11 hormone therapy patients with low baseline PSA value (< 1 ng/ml) from 0.37 down 0.14 ng/ml (p value 0.0068) at one year. Moreover, 14 low risk patients gave better results of mean PSA value than 17 Intermediate risk patients 0.43 ng/ml vs. 0.93 ng/ml (p value 0.02) at one year. No patient had biochemical failure at last follow-up. Hypofractionated SBRT appears to have potential against prostate cancer. Low toxicity and encouraging biochemical control support its use in early-stage prostate cancer. Results encourage further follow-up and larger studies.

Here we report results from the first cohort of over 100 patients treated with hypofractionated, stereotactic body radiotherapy (SBRT) for early stage prostate cancer. Between February 2005 and December 2006, 112 patients with localized, biopsy-proven adenocarcinoma of the prostate (clinical stage T1cN0M0 to T2cN0M0) were treated in Naples, FL on a CyberKnife system (Accuray Incorporated, Sunnyvale, CA). Eighty-one patients had a Gleason score of 3+3. Mean initial PSA was 6.0, and mean initial prostate volume was 46.3cc. Implanted gold fiducials were used for image-guided targeting and tracking. Patients received 35–36 Gy administered in 5 consecutive fractions to the prostate and the proximal seminal vesicles, as identified on CT and MRI scans. At a median follow-up of 24 months, the mean PSA value was 0.78 ng/ml. Two patients have developed biopsy-confirmed local relapse; one developed distant metastases. Acute side effects were generally mild and resolved shortly after treatment. A single Grade 3 rectal complication was reported (bleeding). Eighty-two percent of patients who were sexually potent before treatment maintained erectile function post-treatment. Additional follow-up is required to better evaluate potential late toxicity and long-term PSA outcomes.

There is a clear dose response for localized prostate cancer radiotherapy and there probably is a radiobiological rationale for hypo-fractionation. Combining the two should maximize tumor control and increase the therapeutic ratio. This study examines the rationale and technical feasibility of CyberKnife radiotherapy (a robotic arm-driven linear accelerator) for localized prostate cancer. Its ability to deliver non-coplanar non-isocentric arcs can yield maximally conformal isodoses. It is the only integrated system capable of target position verification and real-time tracking during delivery of conformal stereotactic radiotherapy.

Inverse planning with the CyberKnife is used to design a course of radiotherapy for localized prostate cancer. Fiducial markers within the gland are used to verify organ position and track organ motion via an orthogonal pair of electronic x-ray imaging devices and provide real-time feedback correction to the robotic arm during delivery. Conformal isodose curves and dose volume histograms (DVH) are used to compare with an optimized Intensity-Modulated Radiotherapy (IMRT) plan actually delivered to the study patient based upon CT scan-derived organ volumes.

The CyberKnife can produce superior DVHs for sparing of rectum and bladder and excellent DVHs for target coverage compared with IMRT, and possesses dose heterogeneities to the same degree as IMRT plans. Because of the significantly longer delivery times required it would be best suited for hypo-fractionated regimens. Such dose regimens might allow for biologically equivalent dose escalation without increased normal tissue toxicity. Since the CyberKnife can verify organ position and motion and correct for this in real-time it is the ideal means of achieving such excellent DVHs without a compromise in doses to normal tissues. These capabilities are essential if one contemplates hypo-fractionated regimens with large dose-per-fraction sizes (>5Gy to 10Gy) and dose-escalation.

Desloratadine, a potent antagonist for human histamine H1 receptor, has been revealed to exhibit antihistaminic activity and anti-inflammatory activity. However, it is not yet known whether desloratadine has any effect on the biological behaviors of tumor cells. In this study, we aimed to investigate the effects of desloratadine on cell growth and invasion in bladder cancer EJ and SW780 cells in vitro. We observed that desloratadine inhibited cell viability of EJ and SW780 cells in a dose- and time-dependent manner. Desloratadine treatment was also revealed to suppress colony-formation ability and induce cell cycle arrest at G1 phase in EJ cells. Desloratadine promoted cell apoptosis via modulating the expression of Bcl-2, Bax, cleaved caspase 3, and cleaved caspase 9 in EJ and SW780 cells. Western blot resulted showed that desloratadine also impaired the expression of autophagy-related proteins, such as Beclin 1, P62, and LC3I/II in EJ and SW780 cells; while autophagy inhibitor LY294002 reversed the effects of desloratadine on these proteins. Moreover, desloratadine remarkably attenuated cell migration and invasion. Furthermore, we illustrated that desloratadine downregulated the expression of N-cadherin, Vimentin, Snail1, and Snail2, while upregulated the expression of E-cadherin in EJ and SW780 cells in vitro. The level of interleukin 6 was reduced in desloratadine-treated cells, while upregulation of interleukin 6 significantly abolished the anticancer activity of desloratadine in cell invasion and Bcl-2, Bax, Beclin1, LC3-I/II, N-cadherin, and E-cadherin expression in EJ cells. Taken together, our data suggest a potential anticancer activity of desloratadine on cell growth and invasion for bladder cancer, which may be mediated by diminishing the epithelial-to-mesenchymal transition and interleukin 6.

Purpose: Microwave ablation has become an alternative treatment for pulmonary ground-glass nodules (GGN) and is widely accepted by clinicians. However, its effect on lung function remains unknown. Therefore, this retrospective study aimed to explore pulmonary function changes and associated risk factors in patients undergoing computed tomography (CT)-guided microwave ablation (MWA) for treating pulmonary GGN. Materials and Methods: Thirty-five patients diagnosed with pulmonary GGN on thin-layer chest CT and enhanced CT were examined. Patients unable or unwilling to undergo thoracoscopic surgery underwent CT-guided simultaneous percutaneous core needle biopsy and MWA. Pulmonary function tests (PFT) were performed before ablation and 3 days and 6 months post-ablation. Forced expiratory volume in one second (FEV1), FEV1%, forced vital capacity (FVC), maximal voluntary ventilation (MVV), and peak expiratory flow (PEF) values pre- and post-MWA were analysed. Linear regression analysis was used to examine the correlation between ablation volume and changes in PFT findings 3 days post-ablation. Associations between patient characteristics, rates of postoperative complications, and PFT findings were analysed. Results: Forty-eight lesions were completely ablated and examined intraoperatively. There were significant differences in pre- and post-operative PFT findings on day 3 but not at 6 months. The mean ablation volume after 3 days of 11.4 ± 6.3 cm³ was positively correlated with changes in FEV1, MVV, and PEF values. Patients’ age (mean, 59.4 ± 13.0 years) positively correlated with changes in PEF values. The rates of change in FVC and MVV values were significantly higher with multiple pulmonary nodules than with isolated pulmonary nodule. PFT findings were similar between patients who experienced or did not experience complications (eg, pneumothorax and pleural effusion). Conclusions: Pulmonary function could be impaired shortly after MWA. PFT findings may correlate with age, ablation volume, and number of ablated lesions. In most patients, pulmonary function returned to the preoperative state after 6 months.