Nina Bougatf

Five-year experience with setup and implementation of an integrated database system for clinical documentation and research

In radiation oncology, where treatment concepts are elaborated in interdisciplinary collaborations, handling distributed, large heterogeneous amounts of data efficiently is very important, yet challenging, for an optimal treatment of the patient as well as for research itself. This becomes a strong focus, as we step into the era of modern personalized medicine, relying on various quantitative data information, thus involving the active contribution of multiple medical specialties. Hence, combining patient data from all involved information systems is inevitable for analyses. Therefore, we introduced a documentation and data management system integrated in the clinical environment for electronic data capture. We discuss our concept and five-year experience of a precise electronic documentation system, with special focus on the challenges we encountered. We specify how such a system can be designed and implemented to plan, tailor and conduct (multicenter) clinical trials, ultimately reaching the best clinical performance, and enhancing interdisciplinary and clinical research.

Connection of European particle therapy centers and generation of a common particle database system within the European ULICE-framework

BackgroundTo establish a common database on particle therapy for the evaluation of clinical studies integrating a large variety of voluminous datasets, different documentation styles, and various information systems, especially in the field of radiation oncology.MethodsWe developed a web-based documentation system for transnational and multicenter clinical studies in particle therapy. 560 patients have been treated from November 2009 to September 2011. Protons, carbon ions or a combination of both, as well as a combination with photons were applied. To date, 12 studies have been initiated and more are in preparation.ResultsIt is possible to immediately access all patient information and exchange, store, process, and visualize text data, any DICOM images and multimedia data. Accessing the system and submitting clinical data is possible for internal and external users. Integrated into the hospital environment, data is imported both manually and automatically. Security and privacy protection as well as data validation and verification are ensured. Studies can be designed to fit individual needs.ConclusionsThe described database provides a basis for documentation of large patient groups with specific and specialized questions to be answered. Having recently begun electronic documentation, it has become apparent that the benefits lie in the user-friendly and timely workflow for documentation. The ultimate goal is a simplification of research work, better study analyses quality and eventually, the improvement of treatment concepts by evaluating the effectiveness of particle therapy.

Sequential proton boost after standard chemoradiation for high-grade glioma

PURPOSE To retrospectively assess the feasibility and safety of a sequential proton boost following conventional chemoradiation in high-grade glioma (HGG). METHOD AND MATERIALS Sixty-six consecutive patients with HGG were treated with 50.0 Gy photons (50.0-50.4 Gy) in 2.0 Gy (1.8-2.0 Gy) fractions, followed by a proton boost with 10 Gy equivalent (Gy(RBE)) in 2.0 Gy(RBE) fractions. Patients were matched one to one with 66 patients with HGG undergoing conventional radiation therapy (RT) with 60.0 Gy photons (59.4-60.0 Gy) in 2.0 Gy fractions (1.8-2.0 Gy). Matching criteria were age, WHO grade, Karnofskys performance status, PTV size, temozolomide therapy (each p > 0.1). The study assessed progression-free survival (PFS), overall survival (OS), acute treatment-related toxicity (CTCAE v.4.03) and pseudoprogression (RANO criteria). RESULTS Median PFS and OS were similar in both treatment groups (bimodality RT, PFS: 8.8 months [2-32 months], OS 19.1 months [4-41 months]; photon-only RT, PFS: 7.2 months [2-39 months], 20.9 months [3-53 months]; p = 0.430 and p = 0.125). The median PTV of the proton boost was significantly smaller than the photon plan PTVs (each p < 0.001). Acute toxicity was mild. Toxicity ≥grade 2 was observed in 6 patients (9%) receiving bimodality RT and 9 patients (14%) receiving photon-only RT. Two types of severe adverse events (CTCAE grade 3) occurred solely in the photon-only group: severe increase in intracranial pressure (5%); and generalized seizures (3%). Pseudoprogression was rare, occurring on average 6 weeks after radiotherapy, and was balanced in both treatment groups (n = 4 each; 8%). CONCLUSION Delivering a proton boost to significantly smaller target volumes when compared to photon-only plans, yielded comparable progression and survival rates at lower CTCAE grade 3 acute toxicity rates. Pseudoprogression occurred rarely and evenly distributed in both treatment groups. Thus, bimodality RT was at least equivalent regarding outcome and potentially superior with respect to toxicity in patients with HGG. SUMMARY Treating patients with HGG with 50.0 Gy photons in 2.0 Gy fractions, followed by a proton boost with 10 Gy(RBE) in 2.0 Gy(RBE) fractions, is safe and feasible. Severe radiation-induced acute toxicity and pseudoprogression were rare in both treatment groups. Therefore, in this clinical setting, combined proton radiotherapy might be beneficial in terms of further risk reduction for treatment-related side effects. Interestingly, treatment volume reduction using a proton boost led to comparable survival and progression rates with decreased severe treatment-related toxicity compared to conventional photon radiotherapy.

Towards secondary use of heterogeneous radio-oncological data for retrospective clinical trials: service-oriented connection of a central research database with image analysis tools

Our overall objective is the utilization of heterogeneous and distributed radio-oncological data in retrospective clinical trials. Previously, we have successfully introduced a central research database for collection of heterogeneous data from distributed systems. The next step is the integration of image analysis tools in the standard retrieval process. Hence, analyses for complex medical questions can be processed automatically and facilitated immensely. In radiation oncology recurrence analysis is a central approach for the evaluation of therapeutic concepts. However, various analysis steps have to be performed like image registration, dose transformation and dose statistics. In this paper we show the integration of image analysis tools in the standard retrieval process by connecting them with our central research database using a service-oriented approach. A concrete problem from recurrence analysis has been selected to prove our concept exemplarily. We implemented service-oriented data collection and analysis tools to use them in a central analysis platform, which is based on a work flow management system. An analysis work flow has been designed that, at first, identifies patients in the research database fulfilling the inclusion criteria. Then the relevant imaging data is collected. Finally the imaging data is analyzed automatically. After the successful work flow execution, the results are available for further evaluation by a physician. As a result, the central research database has been connected successfully with automatic data collection and image analysis tools and the feasibility of our service-oriented approach has been demonstrated. In conclusion, our approach will simplify retrospective clinical trials in our department in future.

Do Increased Doses to Stem-Cell Niches during Radiation Therapy Improve Glioblastoma Survival?

Background and Purpose. The reasons for the inevitable glioblastoma recurrence are yet understood. However, recent data suggest that tumor cancer stem cells (CSCs) in the stem-cell niches, with self-renewing capacities, might be responsible for tumor initiation, propagation, and recurrence. We aimed to analyze the effect of higher radiation doses to the stem-cell niches on progression-free survival (PFS) and overall survival (OS) in glioblastoma patients. Materials and Methods. Sixty-five patients with primary glioblastoma treated with radiation therapy were included in this retrospective analysis. The SVZ and DG were segmented on treatment planning magnetic resonance imaging, and the dose distributions to the structures were calculated. The relationship of dosimetry data and survival was evaluated using the Cox regression analysis. Results. Conventionally fractionated patients (n = 54) who received higher doses (D mean ≥ 40 Gy) to the IL SVZ showed improved PFS (8.5 versus 5.2 months; p = 0.013). Furthermore, higher doses (D mean ≥ 30 Gy) to the CL SVZ were associated with increased PFS (10.1 versus 6.9 months; p = 0.025). Conclusion. Moderate higher IL SVZ doses (≥40 Gy) and CL SVZ doses (≥30 Gy) are associated with improved PFS. Higher doses to the DG, the second stem-cell niche, did not influence the survival. Targeting the potential cancer stem cells in the SVZ might be a promising treatment approach for glioblastoma and should be addressed in a prospective randomized trial.

Web-based Documentation System with Exchange of DICOM RT for Multicenter Clinical Studies in Particle Therapy

Conducting clinical studies is rather difficult because of the large variety of voluminous datasets, different documentation styles, and various information systems, especially in radiation oncology. In this paper, we describe our development of a web-based documentation system with first approaches of automatic statistical analyses for transnational and multicenter clinical studies in particle therapy. It is possible to have immediate access to all patient information and exchange, store, process, and visualize text data, all types of DICOM images, especially DICOM RT, and any other multimedia data. Accessing the documentation system and submitting clinical data is possible for internal and external users (e.g. referring physicians from abroad, who are seeking the new technique of particle therapy for their patients). Thereby, security and privacy protection is ensured with the encrypted https protocol, client certificates, and an application gateway. Furthermore, all data can be pseudonymized. Integrated into the existing hospital environment, patient data is imported via various interfaces over HL7-messages and DICOM. Several further features replace manual input wherever possible and ensure data quality and entirety. With a form generator, studies can be individually designed to fit specific needs. By including all treated patients (also non-study patients), we gain the possibility for overall large-scale, retrospective analyses. Having recently begun documentation of our first six clinical studies, it has become apparent that the benefits lie in the simplification of research work, better study analyses quality and ultimately, the improvement of treatment concepts by evaluating the effectiveness of particle therapy.

Oncologic Therapy Support Via Means of a Dedicated Mobile App (OPTIMISE-1): Protocol for a Prospective Pilot Trial

Background The increasing role of consumer electronics and Web-enabled mobile devices in the medical sector opens up promising possibilities for integrating novel technical solutions into therapy and patient support for oncologic illnesses. A recent survey carried out at Heidelberg University Hospital suggested a high acceptance among patients for an additional approach to patient care during radiotherapy based on patient-reported outcomes by a dedicated mobile app. Objective The aim of this trial (OPTIMISE-1: Oncologic Therapy Support Via Means of a Dedicated Mobile App – A Prospective Feasibility Evaluation) is to prospectively evaluate the feasibility of employing a mobile app for the systematic support of radiooncological patients throughout the course of their radiotherapy by monitoring symptoms and patient performance, and facilitating the background-exchange of relevant information between patient and physician. Methods The present single-center, prospective, exploratory trial, conducted at Heidelberg University Hospital, assesses the feasibility of integrating an app-based approach into patient-care during radiotherapy. Patients undergoing curative radiotherapy for thoracic or pelvic tumors will be surveyed regarding general performance, treatment-related quality of life (QoL) and symptoms, and their need to personally consult a physician by means of a mobile app during treatment. The primary endpoint of feasibility will be reached when 80% of the patients have successfully answered 80% of their respective questions scheduled for each treatment day. Furthermore, treatment-related patient satisfaction and health-related QoL is assessed by the Patient Satisfaction Questionnaire Short Form (PSQ-18) and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires at the beginning (baseline) and end of radiotherapy, and at the first follow-up. Results This trial will recruit 50 patients over a period of 12 months. Follow-up will be completed after 18 months, and publication of results is planned at 24 months after trial initiation. Conclusions This study will serve as a basis for future studies aiming to exploit the constant innovation in mobile medical appliances and integrate novel patient-centered concepts into patient care in the context of radiotherapy. Trial Registration ClinicalTrials.gov NCT03168048; https://clinicaltrials.gov/ct2/show/NCT03168048 (Archived at WebCite http://www.webcitation.org/6wtWGgi0X)

High control rates of proton- and carbon-ion-beam treatment with intensity-modulated active raster scanning in 101 patients with skull base chondrosarcoma at the Heidelberg Ion Beam Therapy Center: Particle Therapy for Skull Base Chondrosarcoma

The current study compares the results of irradiation with protons and irradiation with carbon ions via a raster scan technique in patients with G1 and G2 skull base chondrosarcomas.

Independent validation of a new reirradiation risk score (RRRS) for glioma patients predicting post-recurrence survival: A multicenter DKTK/ROG analysis

BACKGROUND AND PURPOSE Reirradiation (reRT) is a valid option with considerable efficacy in patients with recurrent high-grade glioma, but it is still not known which patients might be optimal candidates for a second course of irradiation. This study validated a newly developed prognostic score independently in an external patient cohort. MATERIAL AND METHODS The reRT risk score (RRRS) is based on a linear combination of initial histology, clinical performance status, and age derived from a multivariable model of 353 patients. This score can predict post-recurrence survival (PRS) after reRT. The validation dataset consisted of 212 patients. RESULTS The RRRS differentiates three prognostic groups. Discrimination and calibration were maintained in the validation group. Median PRS times in the development cohort for the good/intermediate/poor risk categories were 14.2, 9.1, and 5.3 months, respectively. The respective groups within the validation cohort displayed median PRS times of 13.8, 8.8, and 3.8 months, respectively. Unos C for development data was 0.64 (CI: 0.60-0.69) and for validation data 0.63 (CI: 0.58-0.68). CONCLUSIONS The RRRS has been successfully validated in an independent patient cohort. This linear combination of three easily determined clinicopathological factors allows for a reliable classification of patients and may be used as stratification factor for future trials.

Supportive Care in Radiotherapy Based on a Mobile App: Prospective Multicenter Survey

Background Consumer electronics and Web-enabled mobile devices are playing an increasing role in patient care, and their use in the oncologic sector opens up promising possibilities in the fields of supportive cancer care and systematic patient follow-up. Objective The objective of our study was to assess the acceptance and possible benefits of a mobile app–based concept for supportive care of cancer patients undergoing radiotherapy. Methods In total, 975 patients presenting for radiotherapy due to breast or prostate cancer were screened; of them, 200 owned a smartphone and consented to participate in the survey. Patients were requested to complete a questionnaire at 2 time points: prior to the initiation (T0) and after the completion (T1) of radiotherapy. The questionnaire included questions about the habits of smartphone usage, technical knowledge and abilities of the participants, readiness to use a mobile app within the context of radiotherapy, possible features of the mobile app, and general attitude toward the different aspects of oncologic treatments. For quantitative analysis, sum scores were calculated for all areas of interest, and results were correlated with patient characteristics. Additionally, answers were quantitatively compared between time points T0 and T1. Results Median patient age was 57 (range 27-78) years. Of the 200 participants, 131 (66.2%) reported having the ability to use their smartphones with minimal to no help and 75.8% (150/200) had not used their smartphones in a medical context before. However, 73.3% (146/200) and 83.4% (166/200) of patients showed a strong interest in using a mobile app for supportive care during radiotherapy and as part of the clinical follow-up, respectively. Patients most commonly requested functionalities regarding appointment scheduling in the clinic (176/200, 88.0%) and the collection of patient-reported outcome data regarding their illness, therapy, and general well-being (130/200, 65.0%). Age was identified as the most influential factor regarding patient attitude, with patients aged <55 years being significantly more inclined toward and versed in smartphone use (P<.001). The acceptance of mobile apps was significantly higher in patients exhibiting a Karnofsky performance index <80% (P=.01). Support in the context of therapy-related side effects was judged most important by patients with poor clinical performance (P=.006). The overall acceptance of mobile apps in the context of radiotherapy surveillance was high at a median item sum score of 71.4/100 and was not significantly influenced by tumor stage, age, gender, treatment setting, or previous radiotherapies. Conclusions The acceptance of mobile apps for the surveillance and follow-up of cancer patients undergoing radiotherapy is high; this high acceptance level will serve as a basis for future clinical trials investigating the clinical benefits of mobile app–based treatment support. Introduction of mobile apps into the clinical routine should be considered as an opportunity to improve and intensify supportive treatment for cancer patients.