Anderson Cancer Center at Cooper

Camden, NJ, United States

Anderson Cancer Center at Cooper

Camden, NJ, United States
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Bailey C.P.,Thomas Jefferson University | Budak-Alpdogan T.,Anderson Cancer Center at Cooper | Sauter C.T.,Thomas Jefferson University | Panis M.M.,Thomas Jefferson University | And 5 more authors.
Oncotarget | Year: 2017

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number of CD8+ T cells (specifically CD44+ memory/activated phenotype) and NK cells. Intracellular IFN-γ and TNF-α secretion by CD8+ T cells increased in the IL-15SA-treated group. IL-15SA also upregulated NKG2D expression on CD8+ T cells. Moreover, IL-15SA enhanced proliferation and cytokine secretion of adoptively transferred CFSE-labeled T cells in syngeneic and allogeneic models by specifically stimulating the slowly proliferative and nonproliferative cells into actively proliferating cells. We then evaluated IL-15SA's effects on anti-tumor activity against murine mastocytoma (P815) and murine B cell lymphoma (A20). IL-15SA enhanced graftversus- tumor (GVT) activity in these tumors following T cell infusion. Interestingly, IL-15 SA administration provided GVT activity against A20 lymphoma cells in the murine donor leukocyte infusion (DLI) model without increasing graft versus host disease. In conclusion, IL-15SA could be a highly potent T- cell lymphoid growth factor and novel immunotherapeutic agent to complement stem cell transplantation and adoptive immunotherapy. © Cavan P. Bailey et al.


Medic I.,Anderson Cancer Center at Cooper | Enriquez M.L.,Anderson Cancer Center at Cooper | Somer R.A.,Anderson Cancer Center at Cooper
Urology Case Reports | Year: 2017

The small intestine is a very uncommon and peculiar site for metastasis from renal cell carcinoma (RCC). We present a clinical presentation of insidious and unusual development of a jejunal metastasis while having stable disease in a remainder of metastatic sites, in a patient undergoing immunotherapy with nivolumab. Due to the extreme rarity of metastatic renal cell carcinoma to the lumen of the small bowel, it is easy to overlook and misdiagnose symptoms of this pathologic entity, particularly when the remainder of metastatic disease responds well to ongoing therapy. © 2017 The Authors


PubMed | First Radiation Oncology Group, Holy Redeemer Hospital and Anderson Cancer Center at Cooper
Type: Journal Article | Journal: Medical physics | Year: 2015

The AAPM TG-135 report is a landmark recommendation for the quality assurance (QA) of image-guided robotic radiosurgery. The purpose of this paper is to present results pertaining to intentionally offsetting the phantom as recommended by TG-135 and to present data on targeting algorithm accuracy as a function of imager parameters in less than ideal circumstances, which had not been available at the time of publication of TG-135.All tests in this study were performed at the Cooper University Hospital CyberKnife Center in Mt. Laurel, NJ. For intentional offsets, initial tests were performed on the Accuray-supplied anthropomorphic head and neck phantom, whereas for subsequent tests, the Accuray-supplied alignment quality assurance (AQA) phantom was used. To simulate the effects of imager parameters for larger patients, slabs of Blue Water (Standard Imaging, Inc., Middleton, WI) were added to attenuate the x-ray images in some of the tests. In conjunction with attenuated x-ray tests, the number of fiducials was varied by systematically deselecting them one at a time at the CyberKnife console.Tests using the AQA phantom verified that submillimeter alignments were consistently achieved even with intentional shifts and rotations of up to 10.0 mm and 1.0, respectively. An analysis of 17 months of daily QA alignment tests showed that submillimeter alignments were achieved more than 99% of the time even with such intentional shifts and rotations of the phantom. When additional slabs of Blue Water were added to simulate patient attenuation of the x-ray images, targeting errors could be induced depending on imager parameters and the amount of Blue Water used. A series of consecutive tests showed that two helpful variables to ensure good accuracy of the system were (1) the fiducial extraction confidence level (FECL) system parameter and (2) the number of targeted fiducials. When fewer than four fiducials were used, the FECL reported by the CyberKnife was sometimes high even when a false lock occurred, so using multiple fiducials helped to ensure reliable targeting.Radiosurgery requires the highest degree of targeting accuracy, and in our experience, the CyberKnife has been able to maintain submillimeter accuracy consistently. It has been verified that our CyberKnife can correct for phantom shifts of up to 10.0 mm and rotations of up to 1.0. It has also been discovered that false locks are more likely to occur with a single fiducial than with multiple fiducials. Although targeting accuracy can only be measured on a phantom, the insight gained from analyzing the QA tests can help us in devising better strategies for achieving the best treatment for our patients.


PubMed | University of Colorado at Denver, Anderson Cancer Center at Cooper, Sloan Kettering Cancer Center, Holy Redeemer Hospital and 6 more.
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2016

To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiation therapy (SBRT) of the thorax.Published studies on lung toxicity in patients with early-stage non-small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT, including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2 to 5 (G2+) and grade 3 to 5 (G3+) RILT were computed. Patient, tumor, and dosimetric factors were analyzed for their correlation with RILT.Eighty-eight studies (7752 patients) that reported RILT incidence were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% confidence interval [CI]: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range, 1.4-4.1) cm. Among the factors analyzed, older patient age (P=.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P=.049) and G3+ RILT (P=.001). Patients with stage IA versus stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, odds ratio=0.43, 95% CI: 0.29-0.64, P<.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P=.027) and V20 (P=.019) in patients with G2+ RILT than in those with grade 0 to 1 RILT.The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD, also significantly affect RILT risk.


PubMed | University of Pennsylvania, Fox Chase Cancer Center, Anderson Cancer Center at Cooper, University of Chicago and 2 more.
Type: Journal Article | Journal: Genetics in medicine : official journal of the American College of Medical Genetics | Year: 2015

Multiplex genetic testing, including both moderate- and high-penetrance genes for cancer susceptibility, is associated with greater uncertainty than traditional testing, presenting challenges to informed consent and genetic counseling. We sought to develop a new model for informed consent and genetic counseling for four ongoing studies.Drawing from professional guidelines, literature, conceptual frameworks, and clinical experience, a multidisciplinary group developed a tiered-binned genetic counseling approach proposed to facilitate informed consent and improve outcomes of cancer susceptibility multiplex testing.In this model, tier 1 indispensable information is presented to all patients. More specific tier 2 information is provided to support variable informational needs among diverse patient populations. Clinically relevant information is binned into groups to minimize information overload, support informed decision making, and facilitate adaptive responses to testing. Seven essential elements of informed consent are provided to address the unique limitations, risks, and uncertainties of multiplex testing.A tiered-binned model for informed consent and genetic counseling has the potential to address the challenges of multiplex testing for cancer susceptibility and to support informed decision making and adaptive responses to testing. Future prospective studies including patient-reported outcomes are needed to inform how to best incorporate multiplex testing for cancer susceptibility into clinical practice.Genet Med 17 6, 485-492.


Xu Q.,Anderson Cancer Center at Cooper | Hanna G.,Anderson Cancer Center at Cooper | Grimm J.,Holy Redeemer Hospital | Kubicek G.,Anderson Cancer Center at Cooper | And 5 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2014

Purpose To quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT). Methods and Materials Twenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections. Results The proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections. Conclusions Accurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an effective surrogate to tumor motion, fiducials provide a close estimation of both rigid and nonrigid motion of liver tumors. The reported displacements could be further utilized for tumor margin definition and motion management in conventional linear accelerator-based liver SBRT. © 2014 Elsevier Inc.


PubMed | First Radiation and Oncology Group, Holy Redeemer, Virtua Fox Chase Cancer Center and Anderson Cancer Center at Cooper
Type: Journal Article | Journal: Medical physics | Year: 2016

To quantitatively evaluate rigid and nonrigid motion of liver tumors based on fiducial tracking in 3D by stereo imaging during CyberKnife SBRT.Twenty-five liver patients previously treated with three-fractions of SBRT were retrospectively recruited in this study. During treatment, the 3D locations of fiducials were reported by the CyberKnife system after two orthogonal kV X-ray images were taken and further validated by geometry derivations. A total of 5004 pairs of X-ray images acquired during the course of treatment for all the patients, were analyzed. For rigid motion, the rotational angles and translational shifts by aligning 3D fiducial groups in different image pairs after least-square fitting were reported. For nonrigid motion, the relative interfractional tumor shape variations were reported and correlated to the sum of inter-fiducial distances. The individual fiducial displacements were also reported after rigid corrections and without angle corrections.The relative tumor volume variation indicated by the inter-fiducial distances demonstrated an increasing trend in the second (101.63.4%) and third fraction (101.25.6%) among most patients. The cause could be possibly due to radiation-induced edema. For all the patients, the translational shift was 8.15.7 mm, with shifts in LR, AP and SI were 2.12.4 mm, 2.82.9 mm and 6.75.1 mm, respectively. The greatest translation shift occurred in SI, mainly due the breathing motion of diaphragm The rotational angles were 1.11.7, 1.92.6 and 1.62.2, in roll, pitch, and yaw, respectively. The 3D fiducial displacement with rigid corrections were 0.20.2 mm and increased to 0.60.3 mm without rotational corrections.The fiducial locations in 3D can be precisely reconstructed from CyberKnife stereo imaging system during treatment. The fiducials provide close estimation of both rigid and nonrigid motion of .liver tumors. The reported data could be further utilized for tumor margin design and motion management in in conventional linac-based treatments.


PubMed | Anderson Cancer Center at Cooper
Type: Journal Article | Journal: Medical physics | Year: 2016

Elekta Infinity is the one of the latest generation LINAC with unique features. Two Infinity LINACs are recently commissioned at our institution. The dosimetric and mechanical characteristics of the machines are presented.Both Infinity LINACs with Agility MLC (160 leaves with 0.5 cm leaf width) are configured with five electron energies (6, 9, 12, 15, and 18 MeV) and two photon energies (6 and 15 MV). One machine has additional photon energy (10 MV). The commissioning was performed by following the manufacturers specifications and AAPM TG recommendations. Beam data of both electron and photon beams are measured with scanning ion chambers and linear diode array. Machines are adjusted to have the dosimetrically equivalent characteristics.The commissioning of mechanical and imaging system meets the tolerances by TG recommendations. The PDDThe dosimetric and mechanical characteristics of two Infinity LINACs show good agreements between them. Although the Elekta Infinity has been used in many institutions, the detailed characteristics of the machine have not been reported. This study provides invaluable information to understand the Infinity LINAC and to compare the quality of commissioning data for other LINACs.


PubMed | Anderson Cancer Center at Cooper
Type: Journal Article | Journal: Medical physics | Year: 2017

Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed.1. Knowledge of a wide variety of markers 2. Knowledge of their application for different disease sites 3. Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant for Accuray planning service.


PubMed | University of Texas M. D. Anderson Cancer Center and Anderson Cancer Center at Cooper
Type: Journal Article | Journal: Medical physics | Year: 2017

Newly published medical physics practice guideline (MPPG 5.a.) has set the minimum requirements for commissioning and QA of treatment planning dose calculations. We present our experience in the validation of a commercial treatment planning system based on MPPG 5.a.In addition to tests traditionally performed to commission a model-based dose calculation algorithm, extensive tests were carried out at short and extended SSDs, various depths, oblique gantry angles and off-axis conditions to verify the robustness and limitations of a dose calculation algorithm. A comparison between measured and calculated dose was performed based on validation tests and evaluation criteria recommended by MPPG 5.a. An ion chamber was used for the measurement of dose at points of interest, and diodes were used for photon IMRT/VMAT validations. Dose profiles were measured with a three-dimensional scanning system and calculated in the TPS using a virtual water phantom.Calculated and measured absolute dose profiles were compared at each specified SSD and depth for open fields. The disagreement is easily identifiable with the difference curve. Subtle discrepancy has revealed the limitation of the measurement, e.g., a spike at the high dose region and an asymmetrical penumbra observed on the tests with an oblique MLC beam. The excellent results we had (> 98% pass rate on 3%/3mm gamma index) on the end-to-end tests for both IMRT and VMAT are attributed to the quality beam data and the good understanding of the modeling. The limitation of the model and the uncertainty of measurement were considered when comparing the results.The extensive tests recommended by the MPPG encourage us to understand the accuracy and limitations of a dose algorithm as well as the uncertainty of measurement. Our experience has shown how the suggested tests can be performed effectively to validate dose calculation models.

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