Predicting the need for massive transfusion: Prospective validation of a smartphone-based clinical decision support tool.

BACKGROUND: Improper or delayed activation of a massive transfusion protocol may have consequences to individuals and institutions. We designed a complex predictive algorithm that was packaged within a smartphone application. We hypothesized it would accurately assess the need for massive transfusion protocol activation and assist clinicians in that decision. METHODS: We prospectively enrolled patients at an urban, level I trauma center. The application recorded the surgeon's initial opinion for activation and then prompted inputs for the model. The application provided a prediction and recorded the surgeon's final decision on activation. RESULTS: Three hundred and twenty-one patients were enrolled (83% male; 59% penetrating; median Injury Severity Score 9; mean base deficit -4.11). Of 36 massive transfusion protocol activations, 26 had an app prediction of "high" or "moderate" probability. Of these, 4 (15%) patients received <10 u blood as a result of early hemorrhage control. Two hundred and eighty-five patients did not have massive transfusion protocol activated by the surgeon with 27 (9%) patients having "moderate" or "high" likelihood predicted by the application. Twenty-four of these did not require massive transfusion, and all patients had acidosis that unrelated to hemorrhagic shock. For 13 (50%) of the patients with "high" probability, the surgeon correctly altered their initial decision based on this information. The algorithm demonstrated an adjusted accuracy of 0.96 (95% confidence interval [0.93-0.98); P ≤ .001]), sensitivity = 0.99, specificity 0.72, positive predictive value 0.96, negative predictive value 0.99, and area under the receiver operating curve = 0.86. CONCLUSION: A smartphone-based clinical decision tools can aid surgeons in the decision to active massive transfusion protocol in real time, although it does not completely replace clinician judgment.

The Uniformed Services University's Surgical Critical Care Initiative (SC2i): Bringing Precision Medicine to the Critically Ill.

Precision medicine endeavors to leverage all available medical data in pursuit of individualized diagnostic and therapeutic plans to improve patient outcomes in a cost-effective manner. Its promise in the field of critical care remains incompletely realized. The Department of Defense has a vested interest in advancing precision medicine for those sent into harm's way and specifically seeks means of individualizing care in the context of complex and highly dynamic combat clinical decision environments. Building on legacy research efforts conducted during the Afghanistan and Iraq conflicts, the Uniformed Service University (USU) launched the Surgical Critical Care Initiative (SC2i) in 2013 to develop clinical- and biomarker-driven Clinical Decision Support Systems (CDSS), with the goals of improving both patient-specific outcomes and resource utilization for conditions with a high risk of morbidity or mortality. Despite technical and regulatory challenges, this military-civilian partnership is beginning to deliver on the promise of personalized care, organizing and analyzing sizable, real-time medical data sets to support complex clinical decision-making across critical and surgical care disciplines. We present the SC2i experience as a generalizable template for the national integration of federal and non-federal research databanks to foster critical and surgical care precision medicine.

Precision diagnosis: a view of the clinical decision support systems (CDSS) landscape through the lens of critical care.

Improving diagnosis and treatment depends on clinical monitoring and computing. Clinical decision support systems (CDSS) have been in existence for over 50 years. While the literature points to positive impacts on quality and patient safety, outcomes, and the avoidance of medical errors, technical and regulatory challenges continue to retard their rate of integration into clinical care processes and thus delay the refinement of diagnoses towards personalized care. We conducted a systematic review of pertinent articles in the MEDLINE, US Department of Health and Human Services, Agency for Health Research and Quality, and US Food and Drug Administration databases, using a Boolean approach to combine terms germane to the discussion (clinical decision support, tools, systems, critical care, trauma, outcome, cost savings, NSQIP, APACHE, SOFA, ICU, and diagnostics). References were selected on the basis of both temporal and thematic relevance, and subsequently aggregated around four distinct themes: the uses of CDSS in the critical and surgical care settings, clinical insertion challenges, utilization leading to cost-savings, and regulatory concerns. Precision diagnosis is the accurate and timely explanation of each patient's health problem and further requires communication of that explanation to patients and surrogate decision-makers. Both accuracy and timeliness are essential to critical care, yet computed decision support systems (CDSS) are scarce. The limitation arises from the technical complexity associated with integrating and filtering large data sets from diverse sources. Provider mistrust and resistance coupled with the absence of clear guidance from regulatory bodies further retard acceptance of CDSS. While challenges to develop and deploy CDSS are substantial, the clinical, quality, and economic impacts warrant the effort, especially in disciplines requiring complex decision-making, such as critical and surgical care. Improving diagnosis in health care requires accumulation, validation and transformation of data into actionable information. The aggregate of those processes-CDSS-is currently primitive. Despite technical and regulatory challenges, the apparent clinical and economic utilities of CDSS must lead to greater engagement. These tools play the key role in realizing the vision of a more 'personalized medicine', one characterized by individualized precision diagnosis rather than population-based risk-stratification.

Bringing the heavy: carbon ion therapy in the radiobiological and clinical context.

Radiotherapy for the treatment of cancer is undergoing an evolution, shifting to the use of heavier ion species. For a plethora of malignancies, current radiotherapy using photons or protons yields marginal benefits in local control and survival. One hypothesis is that these malignancies have acquired, or are inherently radioresistant to low LET radiation. In the last decade, carbon ion radiotherapy facilities have slowly been constructed in Europe and Asia, demonstrating favorable results for many of the malignancies that do poorly with conventional radiotherapy. However, from a radiobiological perspective, much of how this modality works in overcoming radioresistance, and extending local control and survival are not yet fully understood. In this review, we will explain from a radiobiological perspective how carbon ion radiotherapy can overcome the classical and recently postulated contributors of radioresistance (α/ß ratio, hypoxia, cell proliferation, the tumor microenvironment and metabolism, and cancer stem cells). Furthermore, we will make recommendations on the important factors to consider, such as anatomical location, in the future design and implementation of clinical trials. With the existing data available we believe that the expansion of carbon ion facilities into the United States is warranted.

Enhanced dosimetry procedures and assessment for EBT2 radiochromic film.

PURPOSE: Quantitatively determine an optimum image analysis procedure to mitigate inhomogeneities within the EBT2 film and from scanning for accurate absolute dose measurement deposited by an external radiation therapy beam. Multichannel dosimetry procedures were conceived, described, and quantitatively tested against single and dual channel dosimetry. METHODS: A solid water(TM) block was placed on CT imaging and treatment tables in a configuration that avoids bulky compressive devices. CT markers helped register the CT to the treatment plan and the radiation dose distribution from the radiochromic film. The CT images were digitally rotated and resampled to match the spatial resolution of the scanned dosimetric distribution and treatment plan. The ECLIPSE treatment plan planes were digitally translated through digital triangulation of the treatment isocenter to the CT markers in the CT image. A 6 MV photon beam, conforming to the treatment plan, irradiated the EBT2 film sandwiched between solid water(TM) slabs. The exposed radiochromic film images were rotated and translated to the CT images using coincident markers in the CT image that are associated with "tattoos" marked on the radiochromic film. The exposed radiochromic film gray-levels from a flatbed scanner in reflection mode were converted to dose using calibration films. The test dose distribution was scanned and averaged six times to reduce temporal noise. This study generated dose distributions using the red channel alone, green channel alone, ratio of the red to blue channel, ratio of the green to blue channel, a hybrid approach combining the green to blue ratio for higher doses (>80 cGy) with the red to blue ratio (<80 cGy), multichannel averaging and optimized autonomous multichannel correction. Single channel, multichannel, and channel ratio methods for processing the exposed radiochromic film were compared to the treatment plan via gamma analysis. The ellipsoidal decision surface was defined by its axes of 3% of the maximum dose and 3 mm in the horizontal and vertical directions. RESULTS: The multichannel dosimetry procedures provided excellent agreement with calculation of the dose distribution as determined by the gamma analysis. The green channel mostly performed as well or better than the red channel. The green to blue channel ratio for doses when combined with red to blue ratio ("Hybrid") achieved a high level performance. In addition, new registration procedures were developed and tested for aiding the comparison of calculated and experimentally determined dose distributions. CONCLUSIONS: This study described, developed, and tested new processing methods for reducing inaccuracies in absolute dose determination due to inhomogeneities within the film and from scanning. This study found better performance using optimized multichannel following averaging of all color channels. Combining the channel ratios in a hybrid approach also achieved high performance. Averaging the test films reduced temporal noise that severely degraded the blue channel. This methodology avoided using cumbersome, registered correction matrices. Novel registration and digital rotation of CT images enabled quantitative testing and helped improve contact between the radiochromic film and phantom.

Fiducial markers in prostate for kV imaging: quantification of visibility and optimization of imaging conditions.

The purpose of this work is to investigate possible smaller, less-dense fiducial markers implantable into the prostate for target localization and patient repositioning verification in an on-board kV-kV imaging system on a proton gantry. The experiments used a pelvic phantom and a variety of commercially available fiducial markers: CIVCO carbon marker of ϕ; 1 × 3 mm, gold seed markers of ϕ; 0.8 × 3 mm and ϕ; 1.2 × 3 mm, and IBA Visicoil helical gold linear markers in diameters of 0.35, 0.50, 0.75 and 1.15 mm. Two orthogonal on-board kV imagers were arranged for digital radiographic imaging of the phantom through the lateral and anterior-posterior directions. The contrast-to-noise ratio (CNR) for a given marker was calculated and used as a quantitative measure of its visibility. The patient entrance skin exposure (ESE) was measured and parameterized for kVp, mAs and source-to-surface distance. The ratio of CNR to ESE was first introduced to characterize the efficiency for imaging a marker using a given x-ray technique in order to optimize the marker's visibility and simultaneously minimize the x-ray imaging dose. If CNR > 2, which corresponds to a significance p < 0.05, is required for acceptable visibility, the carbon marker and the smallest Visicoil marker are not suitable for imaging through dense bone but the others are capable of being employed in the clinic. It is predicted that other markers in development should have a greater thickness than equivalent of 0.14 mm thick gold in order to produce the acceptable visibility in the lateral kV imaging. The linear Visicoil marker of ϕ; 0.50 × 5 mm is most suitable for kV imaging in the prostate for proton therapy as it induces the least proton dose perturbation amongst the acceptable markers. An optimal range of 120-130 kVp and 40-80 mAs is determined using the maximal CNR/ESE and CNR > 2 for laterally imaging this marker in the prostate.

Predicted rates of secondary malignancies from proton versus photon radiation therapy for stage I seminoma.

PURPOSE: Photon radiotherapy has been the standard adjuvant treatment for stage I seminoma. Single-dose carboplatin therapy and observation have emerged as alternative options due to concerns for acute toxicities and secondary malignancies from radiation. In this institutional review board-approved study, we compared photon and proton radiotherapy for stage I seminoma and the predicted rates of excess secondary malignancies for both treatment modalities. METHODS AND MATERIAL: Computed tomography images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapies. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors. RESULTS: Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues, except for the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119 cGy for proton plans vs. 768 cGy for photon plans; p < 0.0001). Significantly more excess secondary cancers per 10,000 patients/year were predicted for photon radiation than for proton radiation to the stomach (4.11; 95% confidence interval [CI], 3.22-5.01), large bowel (0.81; 95% CI, 0.39-1.01), and bladder (0.03; 95% CI, 0.01-0.58), while no difference was demonstrated for radiation to the pancreas (0.02; 95% CI, -0.01-0.06). CONCLUSIONS: For patients with stage I seminoma, proton radiation therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients with a life expectancy of 40 years from the time of radiation treatment with protons instead of photons. Proton radiation therapy also allowed significant sparing of most critical structures examined and warrants further study for patients with seminoma, to decrease radiation-induced toxicity.

Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer.

BACKGROUND AND PURPOSE: Various radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN. MATERIALS AND METHODS: Initial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy. Contouring was performed on both CTs, and plans (n=40 plans) and dose-volume histograms were generated. RESULTS: The mean GTV volume decreased 53.4% with re-simulation. All plans provided comparable PTV coverage. Compared with IMRT, adaptive IMRT significantly reduced the maximum dose to the mandible (p=0.020) and mean doses to the contralateral parotid gland (p=0.049) and larynx (p=0.049). Compared with IMRT and adaptive IMRT, IMPT significantly lowered the maximum doses to the spinal cord (p<0.002 for both) and brainstem (p<0.002 for both) and mean doses to the larynx (p<0.002 for both) and ipsilateral (p=0.004 IMRT, p=0.050 adaptive) and contralateral (p<0.002 IMRT, p=0.010 adaptive) parotid glands. Adaptive IMPT significantly reduced doses to all critical structures compared with IMRT and adaptive IMRT and several critical structures compared with non-adaptive IMPT. CONCLUSIONS: Although adaptive IMRT reduced dose to several normal structures compared with standard IMRT, non-adaptive proton therapy had a more favorable dosimetric profile than IMRT or adaptive IMRT and may obviate the need for adaptive planning. Protons allowed significant sparing of the spinal cord, parotid glands, larynx, and brainstem and should be considered for SCCHN to decrease normal tissue toxicity while still providing optimal tumor coverage.

Improving proton therapy accessibility through seamless electronic integration of remote treatment planning sites.

OBJECTIVES: Proton radiotherapy is a relatively scarce treatment modality in radiation oncology, with only nine centers currently operating in the United States. Funded by Public Law 107-248, the University of Pennsylvania and the Walter Reed Army Medical Center have developed a remote proton radiation therapy solution with the goals of improving access to proton radiation therapy for Department of Defense (DoD) beneficiaries while minimizing treatment delays and time spent away from home/work (time savings of up to 3 weeks per patient). MATERIALS AND METHODS: To meet both Health Insurance Portability and Accountability Act guidelines and the more stringent security restrictions imposed by the DoD, our program developed a hybrid remote proton radiation therapy solution merging a CITRIX server with a JITIC-certified (Joint Interoperability Test Command) desktop videoconferencing unit. This conduit, thoroughly tested over a period of 6 months, integrates both institutions' radiation oncology treatment planning infrastructures into a single entity for DoD patients' treatment planning and delivery. RESULTS: This telemedicine solution enables DoD radiation oncologists and medical physicists the ability to (1) remotely access a proton therapy treatment planning platform, (2) transfer patient plans securely to the University of Pennsylvania patient database, and (3) initiate ad-hoc point-to-point and multipoint videoconferences to dynamically optimize and validate treatment plans. CONCLUSIONS: Our robust and secure remote treatment planning solution grants DoD patients not only access to a state-of-the-art treatment modality, but also participation in the treatment planning process by Walter Reed Army Medical Center radiation oncologists and medical physicists. This telemedicine system has the potential to lead to a greater integration of military treatment facilities and/or satellite clinics into regional proton therapy centers.

A hybrid integrated services digital network-internet protocol solution for resident education.

OBJECTIVE: The purpose of this study was to explore the effectiveness of incorporating Web-based application sharing of virtual medical simulation software within a multipoint video teleconference (VTC) as a training tool in graduate medical education. MATERIALS AND METHODS: National Capital Consortium Radiation Oncology Residency Program resident and attending physicians participated in dosimetry teaching sessions held via VTC using Acrobat Connect application sharing. Residents at remote locations could take turns designing radiation treatments using standard three-dimensional planning software, whereas instructors gave immediate feedback and demonstrated proper techniques. Immediately after each dosimetry lesson, residents were asked to complete a survey that evaluated the effectiveness of the session. At the end of a 3-month trial of using Adobe Connect, residents completed a final survey that compared this teaching technology to the prior VTC-alone method. RESULTS: The mean difference from equality across all quality measures from the weekly survey was 0.8, where 0 indicated neither enhanced nor detracted from the learning experience and 1 indicated a minor enhancement in the learning experience. The mean difference from equality across all measures from the final survey comparing use of application sharing with VTC to VTC alone was 1.5, where 1 indicated slightly better and 2 indicated a somewhat better experience. CONCLUSIONS: The teaching efficacy of multipoint VTC is perceived by medical residents to be more effective when complemented by application-sharing software such as Adobe Acrobat Connect.

Development of a remote proton radiation therapy solution over internet2.

Through our existing partnership, our research program has leveraged the benefits of proton radiation therapy through the development a robust telemedicine solution for remote proton therapy planning. Our proof-of-concept system provides a cost-effective and functional videoconferencing desktop platform for both ad-hoc and scheduled communication, as well as a robust interface for data collaboration (application-sharing of a commercial radiation treatment planning package). Over a 2-year period, our evaluation of this model has highlighted the inherent benefits of this affordable remote treatment planning solution, i.e., (1) giving physicians the ability to remotely participate in refining and generating proton therapy plans via a secure and robust Internet2 VPN tunnel to the University of Pennsylvania's commercial proton treatment planning package; (2) allowing cancer-care providers sending patients to a proton treatment facility to participate in treatment planning decisions by enabling referring or accepting providers to initiate ad-hoc, point-to-point communication with their counterparts to clarify and resolve issues arising before or during patient treatment; and thus (3) allowing stewards of an otherwise highly centralized resource the ability to encourage wider participation with and referrals to sparsely located proton treatment centers by adapting telemedicine techniques that allow sharing of proton therapy planning services. We believe that our elegant and very affordable approach to remote proton treatment planning opens the door to greater worldwide referrals to the scarce resource of proton treatment units and wide-ranging scientific collaboration, both nationally and internationally.