Treatment data and technical process challenges for practical big data efforts in radiation oncology.

The term Big Data has come to encompass a number of concepts and uses within medicine. This paper lays out the relevance and application of large collections of data in the radiation oncology community. We describe the potential importance and uses in clinical practice. The important concepts are then described and how they have been or could be implemented are discussed. Impediments to progress in the collection and use of sufficient quantities of data are also described. Finally, recommendations for how the community can move forward to achieve the potential of big data in radiation oncology are provided.

Unique prefrontal GABA and glutamate disturbances in co-occurring bipolar disorder and alcohol dependence.

Bipolar disorder (BD) and alcohol dependence (AD) frequently co-occur, and co-occurring BD and AD are associated with devastating public health costs. Minimal neurobiological research exists to guide the development of effective treatments for this treatment-resistant population. We believe the present study represents the first investigation of prefrontal gamma-aminobutyric acid (GABA) and glutamate levels in co-occurring BD and current AD. The participants were 78 individuals who met DSM-IV criteria for BD I/II and current AD (n=20), BD I/II alone (n=19), current AD alone (n=20) or no diagnosis (n=19). The participants completed a baseline diagnostic visit, then returned approximately 4 days later for a two-dimensional J-resolved proton magnetic resonance spectroscopy (1H-MRS) acquisition in dorsal anterior cingulate cortex (dACC). All participants were required to demonstrate ⩾1 week of abstinence from alcohol/drugs via serial biomarker testing before 1H-MRS. A 2 × 2 factorial analysis of variance of cerebrospinal fluid (CSF)-corrected GABA/water concentrations demonstrated a significant BD × AD interaction (F=2.91, P<0.05), signifying uniquely low levels of GABA in BD+AD; this effect doubled when the sample was restricted to individuals who consumed alcohol within 2 weeks of 1H-MRS. There were no overall effects of BD/AD on CSF-corrected glutamate/water levels. However, the BD × AD interaction, signifying uniquely low levels of glutamate in BD+AD, approached statistical significance (F=3.83, P=0.06) in individuals who consumed alcohol within 2 weeks of 1H-MRS. The dACC GABA levels were significantly, negatively associated with Barratt Impulsiveness Scale (r=-0.28, P=0.02) and Obsessive Compulsive Drinking Scale (r=-0.35, P<0.01) scores. If replicated, these results may suggest that future treatment studies should preferentially evaluate therapeutics in BD+AD known to increase prefrontal GABA and glutamate levels.

Technical Report: Evaluation of peripheral dose for flattening filter free photon beams.

PURPOSE: To develop a comprehensive peripheral dose (PD) dataset for the two unflattened beams of nominal energy 6 and 10 MV for use in clinical care. METHODS: Measurements were made in a 40 × 120 × 20 cm(3) (width × length × depth) stack of solid water using an ionization chamber at varying depths (dmax, 5, and 10 cm), field sizes (3 × 3 to 30 × 30 cm(2)), and distances from the field edge (5-40 cm). The effects of the multileaf collimator (MLC) and collimator rotation were also evaluated for a 10 × 10 cm(2) field. Using the same phantom geometry, the accuracy of the analytic anisotropic algorithm (AAA) and Acuros dose calculation algorithm was assessed and compared to the measured values. RESULTS: The PDs for both the 6 flattening filter free (FFF) and 10 FFF photon beams were found to decrease with increasing distance from the radiation field edge and the decreasing field size. The measured PD was observed to be higher for the 6 FFF than for the 10 FFF for all field sizes and depths. The impact of collimator rotation was not found to be clinically significant when used in conjunction with MLCs. AAA and Acuros algorithms both underestimated the PD with average errors of -13.6% and -7.8%, respectively, for all field sizes and depths at distances of 5 and 10 cm from the field edge, but the average error was found to increase to nearly -69% at greater distances. CONCLUSIONS: Given the known inaccuracies of peripheral dose calculations, this comprehensive dataset can be used to estimate the out-of-field dose to regions of interest such as organs at risk, electronic implantable devices, and a fetus. While the impact of collimator rotation was not found to significantly decrease PD when used in conjunction with MLCs, results are expected to be machine model and beam energy dependent. It is not recommended to use a treatment planning system to estimate PD due to the underestimation of the out-of-field dose and the inability to calculate dose at extended distances due to the limits of the dose calculation matrix.

Effects of yohimbine and drug cues on impulsivity and attention in cocaine-dependent men and women and sex-matched controls.

BACKGROUND: Deficits in executive function have been associated with risk for relapse. Data from previous studies suggest that relapse may be triggered by stress and drug-paired cues and that there are significant sex differences in the magnitude of these responses. The aim of this study was to examine the impact of the pharmacological stressor and alpha-2 adrenergic receptor antagonist yohimbine and cocaine cues on executive function in cocaine-dependent men and women. METHODS: In a double-blind placebo controlled cross-over study, cocaine-dependent men (n=12), cocaine-dependent women (n=27), control men (n=31) and control women (n=25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Participants performed the Connors' Continuous Performance Test II prior to medication/placebo administration and immediately after each cue exposure session RESULTS: Healthy controls had a significant increase in commission errors under the yohimbine condition [RR (95% CI)=1.1 (1.0-1.3), χ(2)1=2.0, p=0.050]. Cocaine-dependent individuals exhibited a significant decrease in omission errors under the yohimbine condition [RR (95% CI)=0.6 (0.4-0.8), χ(2)1=8.6, p=0.003]. Cocaine-dependent women had more omission errors as compared to cocaine-dependent men regardless of treatment [RR (95% CI)=7.2 (3.6-14.7), χ(2)1=30.1, p<0.001]. Cocaine-dependent women exhibited a slower hit reaction time as compared to cocaine-dependent men [Female 354 ± 13 vs. Male 415 ± 14; t89=2.6, p=0.012]. CONCLUSIONS: These data add to a growing literature demonstrating significant sex differences in behaviors associated with relapse in cocaine-dependent individuals.

Evidence for the continuous latent structure of mania and depression in out-patients with bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

BACKGROUND: Evidence supporting the continuous latent structure of mood phenomena has not been incorporated into psychiatric diagnostic systems, in part because the evidence has been incomplete. For example, no studies have investigated the boundary between 'sick' and 'well' periods in individuals with bipolar disorder, despite agreement that characterization of mood disorders as having a discrete episodic course is inaccurate. The present study examined the validity of mood episode symptom thresholds in out-patients with bipolar disorder using multiple methodologies: taxometrics and information-theoretic latent distribution modeling (ITLDM), to evaluate the continuity/discontinuity of mood symptoms; and structural equation mixture modeling (SEMM), to evaluate the continuity/discontinuity of associations between mood symptoms and general functioning. METHOD: A total of 3721 out-patients with bipolar disorder from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were available for analysis. Data were collected at participants' baseline STEP-BD visit. Taxometric [maximum covariance/means above minus below a cut (MAXCOV/MAMBAC) with simulated comparison data], ITLDM and SEMM methods were applied twice, once to the Montgomery-Åsberg Depression Rating Scale and again to the Young Mania Rating Scale. RESULTS: Taxometric results unequivocally supported a continuous interpretation of the data. ITLDM results favored many valued 'discrete metrical' models, suggesting that mood symptoms have continuous, but potentially non-normally distributed, latent structures in out-patients with bipolar disorder. Finally, SEMM results demonstrated that latent associations between mood symptoms and general functioning were linear. CONCLUSIONS: Results from the present study argue against the validity of DSM mood episode thresholds and argue for a graded continuum of care of bipolar symptom management.

The structure of depression, anxiety and somatic symptoms in primary care.

BACKGROUND: Observed co-morbidity among the mood and anxiety disorders has led to the development of increasingly sophisticated dimensional models to represent the common and unique features of these disorders. Patients often present to primary care settings with a complex mixture of anxiety, depression and somatic symptoms. However, relatively little is known about how somatic symptoms fit into existing dimensional models. METHOD: We examined the structure of 91 anxiety, depression and somatic symptoms in a sample of 5433 primary care patients drawn from 14 countries. One-, two- and three-factor lower-order models were considered; higher-order and hierarchical variants were studied for the best-fitting lower-order model. RESULTS: A hierarchical, bifactor model with all symptoms loading simultaneously on a general factor, along with one of three specific anxiety, depression and somatic factors, was the best-fitting model. The general factor accounted for the bulk of symptom variance and was associated with psychosocial dysfunction. Specific depression and somatic symptom factors accounted for meaningful incremental variance in diagnosis and dysfunction, whereas anxiety variance was associated primarily with the general factor. CONCLUSIONS: The results (a) are consistent with previous studies showing the presence and importance of a broad internalizing or distress factor linking diverse emotional disorders, and (b) extend the bounds of internalizing to include somatic complaints with non-physical etiologies.

SU-E-T-183: Managing and Assessing Patients Receiving Radiotherapy with Implantable Cardiac Devices.

PURPOSE: To assess the effectiveness of the management of patients with cardiac electronic implantable devices (CEIDS) receiving radiotherapy. METHOD AND MATERIALS: In 2005, a formal communication process was established between Radiation Oncology and Cardiac Electrophysiology (EP) for the management of patients with permanent, implantable cardiac devices receiving radiotherapy. The process requires a pre-treatment consult with EP. This information is provided to a medical physicist, who works with the primary radiation oncologist and dosimetrist. Based on the estimated dose to the device, EP and Radiation Oncology will determine the appropriate oversight required for treatment. To assess the effectiveness of this program, a retrospective analysis of patients with implantable cardiac devices receiving radiotherapy between the years 2005 and 2011 was performed. RESULTS: Sixty-nine patients with CEIDs (19 implantable cardioverter defibrillators (ICDs) and 50 pacemakers) were treated in Radiation Oncology between 2005 and 2011. Patients were treated to a variety of sites, including 21 patients treated to multiple sites. Doses were estimated prior to radiotherapy, and in vivo measurements were obtained for patients near or exceeding our institutional device tolerance (ICDs = 1 Gy and ICPs = 2 Gy), or if the device was less than 10 cm from the edge of a treatment field. Of the patients evaluated, there were only two patients with ICD devices which had a partial reset of diagnostic data during their treatment. There were no major device failures of arrhythmia detection or treatment. CONCLUSIONS: Our multi-disciplinary team has worked together to develop a process to manage the care of patients with permanent implantable cardiac devices. There have been few device events noted in our patient cohort. The team will continue to follow our institutional management methodology to assess the appropriate amount of EP care necessary during radiation therapy. Laura Horwood is on the speakers bureau for Medtronic. Frank Pelosi is on the advisory board for Boston Scientific Corp and St. Jude Medical, is receiving an educational grants from Medtronic, St Jude, Boston Scientific, Biotronik, and a research grants from Medtronic.

Evidence for the continuous latent structure of mania in the Epidemiologic Catchment Area from multiple latent structure and construct validation methodologies.

BACKGROUND: Although psychiatric diagnostic systems have conceptualized mania as a discrete phenomenon, appropriate latent structure investigations testing this conceptualization are lacking. In contrast to these diagnostic systems, several influential theories of mania have suggested a continuous conceptualization. The present study examined whether mania has a continuous or discrete latent structure using a comprehensive approach including taxometric, information-theoretic latent distribution modeling (ITLDM) and predictive validity methodologies in the Epidemiologic Catchment Area (ECA) study. METHOD: Eight dichotomous manic symptom items were submitted to a variety of latent structural analyses, including factor analyses, taxometric procedures and ITLDM, in 10105 ECA community participants. In addition, a variety of continuous and discrete models of mania were compared in terms of their relative abilities to predict outcomes (i.e. health service utilization, internalizing and externalizing disorders, and suicidal behavior). RESULTS: Taxometric and ITLDM analyses consistently supported a continuous conceptualization of mania. In ITLDM analyses, a continuous model of mania demonstrated 6.52:1 odds over the best-fitting latent class model (LCM) of mania. Factor analyses suggested that the continuous structure of mania was best represented by a single latent factor. Predictive validity analyses demonstrated a consistent superior ability of continuous models of mania relative to discrete models. CONCLUSIONS: The present study provided three independent lines of support for a continuous conceptualization of mania. The implications of a continuous model of mania are discussed.

A comparison of the predictive abilities of dimensional and categorical models of unipolar depression in the National Comorbidity Survey.

BACKGROUND: Taxometric research on depression has yielded mixed results, with some studies supporting dimensional solutions and others supporting taxonic solutions. Although supplementary tests of construct validity might clarify these mixed findings, to date such analyses have not been reported. The present study represents a follow-up to our previous taxometric study of depression designed to evaluate the relative predictive validities of dimensional and categorical models of depression. METHOD: Two sets of dimensional and categorical models of depression were constructed from the depression items of the Composite International Diagnostic Interview: (1) empirically derived models obtained using latent structure analyses and (2) rationally selected models, including an additive depressive symptoms scale (dimensional) and DSM major depressive episodes (categorical). Both sets of dimensional and categorical models were compared in terms of their abilities to predict various clinically relevant outcomes (psychiatric diagnoses and impairment). RESULTS: Factor analyses suggested a two-factor model ('cognitive-affective' and 'somatic' symptoms) and latent class analyses suggested a three-class model ('severe depression', 'moderate depression' and 'cognitive-affective distress'). In predictive analyses that simultaneously included dimensional and categorical models as predictors, the dimensional models remained significant unique predictors of outcomes while the categorical models did not. CONCLUSIONS: Both dimensional models provided superior predictive validity relative to their categorical counterparts. These results provide construct validity evidence for the dimensional findings from our previous taxometric study and thus inspire confidence in dimensional conceptualizations of depression. It remains for future research to evaluate the construct validity of the taxonic solutions reported in the literature.

Utilizing an electronic portal imaging device to monitor light and radiation field congruence.

A method to investigate light and radiation field congruence utilizing a commercially available amorphous silicon electronic portal imaging device (EPID) was developed. This method employed an EPID, the associated EPI software, and a diamond-shaped template. The template was constructed from a block tray in which Sn/Pb wires, 1 mm in diameter, were embedded into a diamond shaped groove milled into the tray. The collimator jaws of the linac were aligned such that the light field fell directly on the corners of the diamond. A radiation detection algorithm within the EPI software determined the extent of the radiation field. The light and radiation field congruence was evaluated by comparing the vertexes of the diamond reference structure to the detected radiation field. In addition, the digital jaw settings were recorded and later compared to the light field detected on the films and EPIs. Three linear accelerators were tracked for a period ranging from 2-8 months. Light radiation field congruence tests with films and EPIs were comparable, yielding a difference of less than 0.6 mm, well within the allowed 2-mm tolerance. A disparity was observed in the magnitude of the detected light field. The X and Y dimensions of the light field measured with film differed by less than or equal to 1.4 mm from the digital collimator settings, whereas the values extracted from the EPIs differed by up to 2.5 mm. Based on these findings, EPIs were found to be a quick and reliable alternative to film for qualitative and relative analyses.