Technology in Cancer Research & Treatment

Abdominal stereotactic ablative body radiotherapy is aided by motion management strategies to ensure accurate dose delivery as targets such as the kidney are easily influenced by breathing motion. Commercial devices such as compression plates and dual vacuum technology have been demonstrated to reduce the motion of lung and liver tumors. The aim of this study was to evaluate the effectiveness of a dual vacuum system in reducing kidney motion as well to investigate any relationship between abdominal wall motions with kidney motion. Ten healthy volunteers were set up with and without vacuum compression (Elekta BodyFIX^TM) to simulate free and dampened breathing. Ultrasound imaging was used to visualize kidney motion at the same time an abdominal surface marker was monitored using infrared imaging (Varian, Real Time Position Management). The resulting kidney and abdominal motion tracks were imported into motion analysis (Physmo^TM) and custom built software (Matlab) to calculate amplitude of motion independent of shifting baselines. Thirty-four kidney datasets were available for analysis, with six datasets unable to be retrieved. With vacuum compression six out of nine participants showed a mean reduction of kidney motion ranging between 1.6 and 8 mm (p < 0.050). One participant showed an increase in motion of 8.2 mm (p < 0.001) with vacuum compression. Two participants showed no significant change (<1 mm) in kidney motion. No relationship was observed for abdominal wall motion and motion changes in the left kidney (r = 0.345, p = 0.402) or right kidney (r = 0.527, p = 0.145). Vacuum compression reduced kidney motion in the majority of participants; however larger breathing motion can also result from its use. No pattern emerged regarding which patients may benefit from vacuum immobilization as abdominal wall motion was not found to be an adequate surrogate for kidney motion.

The purpose of this study was to evaluate local control and survival in patients with spinal metastases who were treated with stereotactic body radiotherapy (SBRT) using a CyberKnife, with or without a prior history of irradiation, and to identify prognostic factors predicting them. Between August 2008 and November 2012, 59 spinal metastatic lesions in 39 patients were treated with SBRT. Fourteen lesions (23.7%) were re-irradiated to treat recurrence after prior radiotherapy. Patients were treated with a median radiation dose of 27 Gy (range, 18-35 Gy) in a median of three fractions (range, one to five) using the CyberKnife Xsight Spine tracking system. Median planning target volume of the 59 spinal metastatic lesions was 37.4 cm³ (range, 0.9-301.4 cm³). Radiation was prescribed to the median 80% isodose line that encompassed at least 90% of the tumor volume. The revised Tokuhashi scoring system and the Tomita scoring system were adopted to predict survival of patients. Local progression was defined as tumor progression by imaging, or if other therapy such as surgery or re-irradiation was given after SBRT, as salvage treatment. The median follow-up period was 7.4 months (range, 1.1-42.5 months). Four of 59 (6.8%) lesions experienced local progression, and all of them occurred within 1-year. Two of four local progressions occurred in re-irradiated tumors, which received 21 Gy in three fractions. With respect to treatment site-specific survival (TSS), better performance status and no visceral metastases were associated with a superior outcome (p = 0.011 and p = .001, respectively). With respect to overall survival (OS), better performance status was marginally related to superior outcome (p = 0.096). The revised Tokuhashi scoring system and the Tomita scoring system predicted OS and TSS in patients treated with SBRT. Two patients developed vertebral compression fractures at 1.2 and 1.4 months after SBRT with no evidence of tumor progression. There was no radiation-induced myelopathy. SBRT with a CyberKnife is a safe and effective treatment modality to achieve local control in spinal metastases patients, including those with a previous history of conventional RT. SBRT should be considered for those patients with a relatively indolent primary tumor, good performance status, and no visceral metastases. Survival of these patients can potentially be prolonged by long-term control of spinal metastases.

Pediatric cranio-spinal axis irradiation (CSI) is a valuable treatment for many central nervous system (CNS) diseases, but due to the life expectancies and quality of life expectations for children, the minimization of the risk for radiation-induced secondary malignancies must be a high priority. This study compared the estimated CSI-induced secondary malignancy risks of three radiation therapy modalities using three different models. Twenty-four (n = 24) pediatric patients previously treated with CSI for tumors of the CNS were planned using three different treatment modalities: three-dimensional conformal radiation therapy (3D-CRT), volume modulated arc therapy (VMAT), and Tomotherapy. Each plan was designed to deliver 23.4 Gy (1.8 Gy/fraction) to the target which was defined as the entire brain and spinal column with a 0.7 cm expansion. The mean doses as well as the dose volume histograms (DVH) of specific organs were analyzed for secondary malignancy risk according to three different methods: the effective dose equivalent (EDE), the excess relative risk (ERR), and the linear quadratic (LQ) models. Using the EDE model, the average secondary risk was highest for the 3D-CRT plans (37.60%), compared to VMAT (28.05%) and Tomotherapy (27.90%). The ERR model showed similarly that the 3D-CRT plans had considerably higher risk (10.84%) than VMAT and Tomotherapy, which showed almost equal risks (7.05 and 7.07%, respectively). The LQ model requires organ-specific cell survival parameters, which for the lungs, heart, and breast relevant values were found and applied. The lung risk for secondary malignancy was found to be 1.00, 1.96, and 2.07% for 3D-CRT, VMAT, and Tomotherapy, respectively. The secondary cancer risk for breast was estimated to be 0.09, 0.21, and 0.27% and for heart it was 9.75, 6.02 and 6.29% for 3D-CRT, VMAT, and Tomotherapy, respectively. Based on three methods of secondary malignancy estimation, the 3D-CRT plans produced highest radiation-induced secondary malignancy risk, and the VMAT and Tomotherapy plans had nearly equal risk. Pediatric patients must be treated with reducing long term sequelae as a priority.

We aimed to assess the dosimetric impact of advanced delivery radiotherapy techniques using either intensity modulated x-ray beams (IMXT), volumetric modulated arc therapy (VMAT), or intensity modulated proton therapy (IMPT), for high-risk prostate cancer patients with sentinel nodes in the pararectal region. Twenty high-risk prostate cancer patients were included in a prospective trial evaluating sentinel nodes on pelvic SPECT acquisition. To be eligible for the dosimetric study, patients had to present with pararectal sentinel nodes usually not included in the clinical target volume encompassing the pelvic lymph nodes. Radiotherapy-plans including the prostate, the seminal vesicles, and the pelvic lymph nodes with the pararectal sentinel nodes were optimized for 6 eligible patients. IMXT and IMPT were delivered with 7 and 3 beams respectively and VMAT with 2 arcs. Results were assessed with Dose-Volume Histograms and predictive normal tissue complication probabilities (NTCPs) models between the three competing treatment modalities aiming to deliver a total dose of 50.4 Gy in 1.8 Gy daily fractions. Target coverage was optimized with IMPT when compared to IMXT and VMAT. Coverage of the sentinel node was slightly better with IMXT (D_98% 5 57.3 ± 5.1 Gy) when compared with VMAT (D_98% 5 56.2 ± 4.1 Gy). The irradiation of rectal, bladder, small bowel, and femoral heads volumes was significantly reduced with IMPT when compared to IMXT and VMAT. NTCPs rates for rectal and bladder ≥ grade-3 late toxicity were better with IMPT (0.4 ± 0.0% and 0.0 ± 0.0%) compared with IMXT (4.6 ± 3.3% and 1.4 ± 1.1%), and VMAT (4.5 ± 4.0% and 1.6 ± 1.6%), respectively. Acceptable dose-volume distributions and low rectal and urinary NTCPs were estimated to geometrically complex pelvic volumes such as the ones proposed in this study using IMXT, VMAT and IMPT. IMPT succeeded, however, to propose the best physical and biological treatment plans compared to both X-ray derived plans.

The purpose of this study was to evaluate the role of diffusion-weighted MR imaging (DW-MRI) in the assessment of treatment response of primary or secondary liver malignancies after stereotactic radiosurgery (SRS) using robotic radiosurgery. All patients who underwent SRS therapy for hepatic malignancies who had pre- and post-interventional MR examinations including DW-MRI at our hospital between 02/2010 and 02/2012 were included. A retrospective analysis of the institutional imaging database identified 13 patients (4 men, 9 women, mean age: 66 years) with a total of 14 primary or secondary liver malignancies. Criteria of tumor response to treatment were a decrease in size and/or loss of contrast enhancement as assessed with respect to RECIST criteria. Mean apparent diffusion coefficient (ADC) values for normal liver parenchyma and hepatic masses in each MR examination were calculated and compared using two-tailed, paired t-test with a significance level of 0.05. Mean ADC values of liver malignancies were 1.10 ± 0.30 x 10^-3 mm2/s, 1.48 ± 0.35 x 10^-3 mm^2/s and 1.56 ± 0.40 x 10^-3 mm^2/s on pre-interventional, the first post-interventional, and the second post-interventional DW-MRI. There was a significant increase of ADC values between the pre-interventional examination and the first and second post-interventional follow-up exams (p < 0.01 and p = 0.01, respectively). However, there was no statistical difference between the ADC values of the first and second post-interventional MRI. ADC values of normal liver parenchyma did not show significant changes in ADC values during pre- and post-interventional MRI. ADC measurements may allow the evaluation of response to treatment of hepatic malignancies by SRS. ADC values of liver malignancies increase significantly after SRS treatment.

This study aimed to analysis outcome and prognosis of interstitial 125I seed implantation in patients with cervical lymph node recurrence after multimodal treatment of thoracic esophageal squamous cell carcinoma (ESCC). We conducted a retrospective review of 19 patients with 32 cervical lymph nodes recurrences after multimodal treatment (lymphadenectomy, radiotherapy, chemotherapy, and various combinations of these treatments) of thoracic ESCC, who underwent ¹²⁵I seed implantation in our department from 2003 to 2011. All the patients were followed up until expiration and the median duration of follow up was 7 months (range, 3-44 months). Syndromes significantly improved after implantation. The local control rates after 3, 6, 12, and 24 months were 84.2%, 63.2%, 32.0%, and 26.0%, respectively, with a median of 10 months. The median overall survival time was 7 months (95% CI, 5.6-8.4), and 1- and 2-year survival rates were 31.6% and 10.5%, respectively. Among these patients, there were 11 died of progression of disease (PD) 3-44 months after implantation. One patient presented grade IV skin toxic effect and repaired by free flap transplantation. No fatal complications such as massive bleeding happened. In univariate analysis, N stage, number of recurrent nodes, recurrence interval time, and D90 were prognostic factors of the tumor local control and survival (p = 0.131 vs. 0.029, 0.129 vs. 0.071, 0.042 vs. 0.042, and 0.056 vs. 0.065, respectively). Multivariate analysis demonstrated that N stage, number of recurrent nodes, and recurrence interval time were independent prognostic factors of the tumor local control (p = 0.022, 0.019, and <0.001, respectively), and recurrence interval time was prognostic factor of the survival (p < 0.001). Interstitial ¹²⁵I seed implantation is a safe and effective salvage treatment for cervical lymph node recurrence after multimodal treatment. The N stage, number of recurrent nodes and recurrence interval time are factors influencing tumor local control, and the recurrence interval time is independent factor influencing survival after percutaneous ¹²⁵I seed implantation in ESCC with cervical lymph node recurrence.

Fluorescence guided surgery (FGS) is a developing field of surgical and oncologic research. Practically, FGS has shown useful applications in urologic surgery, benign biliary surgery, colorectal cancer liver metastasis resection, and ovarian cancer debulking. Most notably in in cancer surgery, FGS allows for the clear delineation of cancerous tissue from benign tissue. FGS requires the utilization of a fluorescent contrast agent and an intraoperative fluorescence imaging device (IFID). Currently available IFIDs are expensive, unable to work with multiple fluorophores, and can be cumbersome. This study aims to describe the development and utility of a small, cost-efficient, and interchangeable IFID made from commercially available components. Extensive research was done to design and construct a light-weight, portable, and cost-effective IFID. We researched the capabilities, size, and cost of several camera types and eventually decided on a near-infrared (NIR) charged couple device (CCD) camera for its overall profile. The small portable interchangeable imager of fluorescence (SPIIF) is a “scout” IFID system for FGS. The main components of the SPIIF are a NIR CCD camera with an articulating light filter. These components and a LED light source with an attached heat sink are mounted on a small metal platform. The system is connected to a laptop by a USB 2.0 cable. Pixielink © software on the laptop runs the system by controlling exposure time, gain, and image capture. After developing the system, we evaluated its utility as an IFID. The system weighs less than two pounds and can cover a large area. Due to its small size, it is easily made sterile by covering it with any sterile plastic sheet. To determine the system’s ability to detect fluorescent signal, we used the SPIIF to detect indocyanine green under ex and in-vivo conditions and fluorescein under ex-vivo conditions. We found the SPIIF was able to detect both ICG and fluorescein under different depths of a semi-opaque colloid. Second, we found that a concentration as low as 0.5 g/ml of indocyanine green dissolved in plasma was detectable. Lastly, in a murine and human cancer model, the SPIIF was able to detect indocyanine green signal within tumors and generate a signal-to-background ratio (SBR) of 3.75. This study shows that a low-cost IFID can be made from commercially available parts. Second, this IFID is capable of in and ex-vivo detection of multiple fluorophores without sacrificing its small size or favorable ergonomics.

Recent advancements in imaging and targeting have expanded the utility of ultrasound therapy with increasing attention being paid to the application of ultrasound in cancer therapy. We present in this article a review of the biological effects of non-thermal ultrasound that could find application in cancer treatment in the near and long term. A careful examination of the ultrasound parameters that elicited these observed effects is needed so that one may refine and apply these results for clinical application. Reported biological effects from non-thermal ultrasound have been categorized into mechanical and chemical means of action. Cavitation and acoustic radiation force are the main contributors to sonomechanical effects of ultrasound while reactive oxygen species contribute to its sonochemical effects. These two categories are responsible for observations such as induction of apoptosis in cancer cells, disturbance of the cytoskeleton, enhancement of gene transfection and chemotherapeutic potency, and modulation of cellular proliferation and protein synthesis. In this review we have considered the biological effects of non-thermal ultrasound, the range of parameters at which these biological effects are observed, and the applicability of the observed biological effects to cancer therapy.

Flow cytometry method (FCM) is a generally accepted tool to analyze apoptosis. Although apoptosis assay kit was applied by many companies, the manufacturers were not consistent with whether using Trypsin with EDTA to collect the adherent cells. In another words, the influence of EDTA on apoptotic ratio is not clear. In this work, we compared the proportion of apoptotic cells with EDTA or EDTA-free Trypsin treatment by FCM. We concluded that Trypsin with or without EDTA has little influence on the proportion of apoptotic cells. In addition, we found that the ratio of necrosis and apoptosis was different in cells collected by scraping. WAVE2 protein was analyzed as a typical example for movement related protein. WAVE2 expression is elevated in the EDTA Trypsin treated group, compared with EDTA-free Trypsin treatment and scrapping group.

While knock-down of glucose transporter protein 1 (GLUT-1) inhibited various human cancer cell growth in vitro and in vivo, including osteosarcoma cell growth in vitro, there has been no report on whether knock-down of GLUT-1 by siRNA may inhibit osteosarcoma cell growth in vivo. We hypothesized that siRNA may inhibit osteosarcoma cell growth in vivo. We introduced siRNA-GLUT-1 by lentivirus into MG63 osteosarcoma cells which were xenograted into nude mice. Immunohistochemical staining, Western blot and reverse transcriptase quantitative (RT-qPCR) were used to determine GLUT-1 protein and mRNA expression of the tumor cells. The results showed the tumor volume of GLUT-1-siRNA-MG63 cells xenorafted nude mice was significantly less than that of siGFP-MG63 or MG63 cells xenografted nude mice (P < 0.05), suggesting that silencing of GLUT-1 inhibited tumor formation and growth of osteosarcoma cells in vivo. Our findings suggest that the lentiviral-mediated siRNA interference against GLUT-1 may be a valuable tool for gene therapy for osteosarcoma.