PubMed | Hackensack University Medical Center, Cone Health, Gibbs Cancer Center and Research Institute and Royal North Shore Hospital
Type: Journal Article | Journal: Medical physics | Year: 2016
To develop a model to analyze medical accelerator generated parameter and performance data that will provide an early warning of performance degradation and impending component failure.A robust 6 MV VMAT quality assurance treatment delivery was used to test the constancy of accelerator performance. The generated text log files were decoded and analyzed using statistical process control (SPC) methodology. The text file data is a single snapshot of energy specific and overall systems parameters. A total of 36 system parameters were monitored which include RF generation, electron gun control, energy control, beam uniformity control, DC voltage generation, and cooling systems. The parameters were analyzed using Individual and Moving Range (I/MR) charts. The chart limits were calculated using a hybrid technique that included the use of the standard 3 limits and the parameter/system specification. Synthetic errors/changes were introduced to determine the initial effectiveness of I/MR charts in detecting relevant changes in operating parameters. The magnitude of the synthetic errors/changes was based on: the value of 1 standard deviation from the mean operating parameter of 483 TB systems, a small fraction ( 5%) of the operating range, or a fraction of the minor fault deviation.There were 34 parameters in which synthetic errors were introduced. There were 2 parameters (radial position steering coil, and positive 24V DC) in which the errors did not exceed the limit of the I/MR chart. The I chart limit was exceeded for all of the remaining parameters (94.2%). The MR chart limit was exceeded in 29 of the 32 parameters (85.3%) in which the I chart limit was exceeded.Statistical process control I/MR evaluation of text log file parameters may be effective in providing an early warning of performance degradation or component failure for digital medical accelerator systems. Research is Supported by Varian Medical Systems, Inc.
PubMed | Hackensack University Medical Center, Cone Health, Gibbs Cancer Center and Research Institute and Royal North Shore Hospital
Type: Journal Article | Journal: Medical physics | Year: 2016
To determine the effectiveness of SPC analysis for a model predictive maintenance process that uses accelerator generated parameter and performance data contained in trajectory log files.Each trajectory file is decoded and a total of 131 axes positions are recorded (collimator jaw position, gantry angle, each MLC, etc.). This raw data is processed and either axis positions are extracted at critical points during the delivery or positional change over time is used to determine axis velocity. The focus of our analysis is the accuracy, reproducibility and fidelity of each axis. A reference positional trace of the gantry and each MLC is used as a motion baseline for cross correlation (CC) analysis. A total of 494 parameters (482 MLC related) were analyzed using Individual and Moving Range (I/MR) charts. The chart limits were calculated using a hybrid technique that included the use of the standard 3 limits and parameter/system specifications. Synthetic errors/changes were introduced to determine the initial effectiveness of I/MR charts in detecting relevant changes in operating parameters. The magnitude of the synthetic errors/changes was based on: TG-142 and published analysis of VMAT delivery accuracy.All errors introduced were detected. Synthetic positional errors of 2mm for collimator jaw and MLC carriage exceeded the chart limits. Gantry speed and each MLC speed are analyzed at two different points in the delivery. Simulated Gantry speed error (0.2 deg/sec) and MLC speed error (0.1 cm/sec) exceeded the speed chart limits. Gantry position error of 0.2 deg was detected by the CC maximum value charts. The MLC position error of 0.1 cm was detected by the CC maximum value location charts for every MLC.SPC I/MR evaluation of trajectory log file parameters may be effective in providing an early warning of performance degradation or component failure for medical accelerator systems.
Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the US National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
PubMed | Hartford Hospital Helen and Harry Gray Cancer Center, Dana-Farber Cancer Institute, Sloan Kettering Cancer Center, U.S. National Cancer Institute and 5 more.
Type: | Journal: Health and quality of life outcomes | Year: 2016
PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system.Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed.103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were 0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS=-0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported no problems responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper.Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration.NCT Clinicaltrials.gov identifier: NCT02158637.
PubMed | Genetics and Pharmacogenomics, H. Lee Moffitt Cancer Center and Research Institute, Molecular Health GmbH, Gibbs Cancer Center and Research Institute and LabCorp
Type: | Journal: Nature communications | Year: 2016
Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinicopathologic staging for decades. There is a need to stratify subpopulations of CRC on a molecular basis to better predict outcome and assign therapies. Here we report targeted exome-sequencing of 1,321 cancer-related genes on 468 tumour specimens, which identified a subset of 17 genes that best classify CRC, with APC playing a central role in predicting overall survival. APC may assume 0, 1 or 2 truncating mutations, each with a striking differential impact on survival. Tumours lacking any APC mutation carry a worse prognosis than single APC mutation tumours; however, two APC mutation tumours with mutant KRAS and TP53 confer the poorest survival among all the subgroups examined. Our study demonstrates a prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC.
PubMed | Hackensack University Medical Center, Cone Health, Gibbs Cancer Center and Research Institute, Medical Center Boulevard and Royal North Shore Hospital
Type: | Journal: Radiation oncology (London, England) | Year: 2016
Unscheduled accelerator downtime can negatively impact the quality of life of patients during their struggle against cancer. Currently digital data accumulated in the accelerator system is not being exploited in a systematic manner to assist in more efficient deployment of service engineering resources. The purpose of this study is to develop an effective process for detecting unexpected deviations in accelerator system operating parameters and/or performance that predicts component failure or system dysfunction and allows maintenance to be performed prior to the actuation of interlocks.The proposed predictive maintenance (PdM) model is as follows: 1) deliver a daily quality assurance (QA) treatment; 2) automatically transfer and interrogate the resulting log files; 3) once baselines are established, subject daily operating and performance values to statistical process control (SPC) analysis; 4) determine if any alarms have been triggered; and 5) alert facility and system service engineers. A robust volumetric modulated arc QA treatment is delivered to establish mean operating values and perform continuous sampling and monitoring using SPC methodology. Chart limits are calculated using a hybrid technique that includes the use of the standard SPC 3 limits and an empirical factor based on the parameter/system specification.There are 7 accelerators currently under active surveillance. Currently 45 parameters plus each MLC leaf (120) are analyzed using Individual and Moving Range (I/MR) charts. The initial warning and alarm rule is as follows: warning (2 out of 3 consecutive values 2 hybrid) and alarm (2 out of 3 consecutive values or 3 out of 5 consecutive values3 hybrid). A customized graphical user interface provides a means to review the SPC charts for each parameter and a visual color code to alert the reviewer of parameter status. Forty-five synthetic errors/changes were introduced to test the effectiveness of our initial chart limits. Forty-three of the forty-five errors (95.6 %) were detected in either the I or MR chart for each of the subsystems monitored.Our PdM model shows promise in providing a means for reducing unscheduled downtime. Long term monitoring will be required to establish the effectiveness of the model.
PubMed | Medical University of South Carolina, Gibbs Cancer Center and Research Institute and University of South Carolina
Type: Comparative Study | Journal: Digestive diseases and sciences | Year: 2016
Compared to whites, blacks have higher colorectal cancer incidence and mortality rates and are at greater risk for early-onset disease. The reasons for this racial disparity are poorly understood, but one contributing factor could be differences in access to high-quality screening and medical care.The present study was carried out to assess whether a racial difference in prevalence of large bowel polyps persists within a poor and uninsured population (n = 233, 124 blacks, 91 whites, 18 other) undergoing screening colonoscopy.Eligible patients were uninsured, asymptomatic, had no personal history of colorectal neoplasia, and were between the ages 45-64 years (blacks) or 50-64 years (whites, other). We examined the prevalence of any adenoma (conventional, serrated) and then difference in adenoma/polyp type by race and age categories.Prevalence for 1 adenoma was 37 % (95 % CI 31-43 %) for all races combined and 36 % in blacks <50 years, 38 % in blacks 50 years, and 35 % in whites. When stratified by race, blacks had a higher prevalence of large conventional proximal neoplasia (8 %) compared to whites (2 %) (p value = 0.06) but a lower prevalence of any serrated-like (blacks 18 %, whites 32 %; p value = 0.02) and sessile serrated adenomas/polyps (blacks 2 %, whites 8 % Chi-square p value; p = 0.05).Within this uninsured population, the overall prevalence of adenomas was high and nearly equal by race, but the racial differences observed between serrated and conventional polyp types emphasize the importance of taking polyp type into account in future research on this topic.
Gersh J.A.,Gibbs Cancer Center and Research Institute |
Gersh J.A.,Spectrum Medical Physics LLC. |
Journal of Applied Clinical Medical Physics | Year: 2015
Traditional CyberKnife (CK) calibration uses TG-51, which requires kQ to be defined using the standard reference condition of 100 cm SSD in a 10 cm × 10 cm field. Since the CK is calibrated using a 6 cm fixed-aperture collimating cone at 80 cm SAD, the BJR-25 method is commonly used to relate circular-field PDDs to square-field PDDs for kQ determination. Using the InCise MLC system, the CK is able to deliver rectangular fields, allowing a more direct measurement of %dd(10cm) using conventional reference conditions. We define the PDD correction factor (CPDD) as the ratio of %dd(10 cm) measured using CK reference conditions to that measured using standard TG-51 reference conditions. Using four ionization chambers (A1SL, CC08, CC13, and A19), %dd(10 cm) is measured using a 6 cm fixed cone at 80 cm SSD and at 100 cm SSD using an effective 10 cm × 10 cm MLC-collimated field. These values are used to calculate CPDD, while the latter is used to directly calculate a kQ value. This direct kQ value is then compared to values determined using the BJR-25 method. Using the MLC system, this study demonstrates conversion between the %dd(10 cm) measured using CyberKnife reference conditions and TG-51 reference conditions. These values provide the means for derivation of a kQ curve as a function of direct measurements of %dd(10cm) using a 6 cm fixed-aperture collimating cone at 80 cm SSD.
Lee C.G.,Gibbs Cancer Center and Research Institute |
McCarthy S.,H. Lee Moffitt Cancer Center and Research Institute |
Gruidl M.,H. Lee Moffitt Cancer Center and Research Institute |
Timme C.,H. Lee Moffitt Cancer Center and Research Institute |
Yeatman T.J.,Gibbs Cancer Center and Research Institute
PLoS ONE | Year: 2014
Background: The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer progression and may promote resistance to therapy. An analysis of patients (n = 71) profiled with both gene expression and a global microRNA assessment (,415 miRs) identified miR-147 as highly anti-correlated with an EMT gene expression signature score and postulated to reverse EMT (MET). Methods and Findings: miR-147 was transfected into colon cancer cells (HCT116, SW480) as well as lung cancer cells (A-549). The cells were assessed for morphological changes, and evaluated for effects on invasion, motility, and the expression of key EMT markers. Resistance to chemotherapy was evaluated by treating cells with gefitinib, an EGFR inhibitor. The downstream genes regulated by miR-147 were assayed using the Affymetrix GeneChip U133 Plus2.0 platform. miR-147 was identified to: 1. cause MET primarily by increasing the expression of CDH1 and decreasing that of ZEB1; 2. inhibit the invasion and motility of cells; 3. cause G1 arrest by up-regulating p27 and down-regulating cyclin D1. miR-147 also dramatically reversed the native drug resistance of the colon cancer cell line HCT116 to gefitinib. miR-147 significantly repressed Akt phosphorylation, and knockdown of Akt with siRNA induced MET. The morphologic effects of miR-147 on cells appear to be attenuated by TGF-B1, promoting a plastic and reversible transition between MET and EMT. Conclusion: miR-147 induced cancer cells to undergo MET and induced cell cycle arrest, suggesting a potential tumor suppressor role. miR-147 strikingly increased the sensitivity to EGFR inhibitor, gefitinib in cell with native resistance. We conclude that miR-147 might have therapeutic potential given its ability to inhibit proliferation, induce MET, as well as reverse drug sensitivity. © 2014 Lee et al.
Kothari N.,H. Lee Moffitt Cancer Center and Research Institute |
Schell M.J.,H. Lee Moffitt Cancer Center and Research Institute |
Teer J.K.,H. Lee Moffitt Cancer Center and Research Institute |
Yeatman T.,Gibbs Cancer Center and Research Institute |
And 2 more authors.
Journal of Clinical Pathology | Year: 2014
Aims: Based on KRAS testing, the subset of patients with metastatic colorectal cancer (CRC) that could benefit from anti-EGFR therapy can be better delineated. Though KRAS testing has become significantly more prevalent over the last few years, methods for testing remain heterogeneous and discordance has been reported between methods. Methods: In this study, we examined a CRC patient population and compared KRAS testing done in Clinical Laboratory Improvement Amendments (CLIA) approved laboratories as part of standard clinical care and by next-generation sequencing (NGS) using the Illumina platform. Discordances were further evaluated with manual review of the NGS testing. Results: Out of 468 CRC patient samples, 77 had KRAS testing done by both CLIA assay and NGS. There were concordant results between testing methodologies in 74 out of 77 patients, or 96% (95% CI 89% to 99%). There were three patient samples that showed discordant results between the two methods of testing. Upon further investigation of the NGS results for the three discordant cases, one sample showed a low level of the mutation seen in the standard testing, one sample showed low tumour fraction and a third did not show any evidence of the mutation that was found with the standard assay. Five patients had KRAS mutations not typically tested with standard testing. Conclusions: Overall there was a high concordance rate between NGS and standard testing for KRAS. However, NGS revealed mutations that are not tested for with standard KRAS assays that might have clinical impact with regards to the role for anti-EGFR therapy.
Bagui T.K.,H. Lee Moffitt Cancer Center and Research Institute |
Sharma S.S.,H. Lee Moffitt Cancer Center and Research Institute |
Sharma S.S.,Gibbs Cancer Center and Research Institute |
Ma L.,H. Lee Moffitt Cancer Center and Research Institute |
And 3 more authors.
Cell Cycle | Year: 2013
Histone deacetylases (HDACs) are important determinants of gene transcription and other biological processes. HDAC11 is one of the least characterized HDACs and is the only member of the class IV HDAC family. Our studies examined the events that control the expression of the HDAC11 transcript. We show that platelet-derived growth factor (PDGF) rapidly reduces the abundance of HDAC11 mRNA when added to density-arrested Balb/c-3T3 cells, which are nontransformed fibroblasts. Reduction required mRNA and protein synthesis, but not AKt or ERK activity, and resulted from accelerated turnover of the HDAC11 transcript. Reduction was transient in cells receiving PDGF alone but sustained in cells receiving both PDGF and platelet-poor plasma, which together promote G0/G1 traverse and S phase entry. Plasma alone did not appreciably reduce HDAC11 mRNA abundance, nor did epidermal growth factor, insulin-like growth factor, or insulin. HDAC11 mRNA accumulated in Balb/c-3T3 cells exiting the cell cycle due to density-dependent growth inhibition or serum deprivation. of note, HDAC11 mRNA did not accumulate in a spontaneously transformed Balb/c-3T3 clonal variant (clone 2) that does not density arrest. the HDAC11 promoter was active in Balb/c-3t3 but not clone 2 cells; inactivity in clone 2 cells did not result from methylation of CpG islands. Overexpression of HDAC11 inhibited the cell cycle progression of both transformed and nontransformed fibroblasts. Our studies identify the HDAC11 transcript as a PDGF target and show that HDAC11 mRNA abundance correlates inversely with proliferative status. © 2013 Landes Bioscience.