Kerstin A. Kessel

Acute Toxicity and Quality of Life in Patients With Prostate Cancer Treated With Protons or Carbon Ions in a Prospective Randomized Phase II Study--The IPI Trial.

PURPOSE The purpose of this study was to compare safety and feasibility of proton therapy with that of carbon ion therapy in hypofractionated raster-scanned irradiation of the prostate, in a prospective randomized phase 2 trial. METHODS AND MATERIALS In this trial, 92 patients with localized prostate cancer were enrolled. Patients were randomized to receive either proton therapy (arm A) or carbon ion therapy (arm B) and treated with a total dose of 66 Gy(relative biological effectiveness [RBE]) administered in 20 fractions (single dose of 3.3 Gy[RBE]). Patients were stratified by the use of antihormone therapy. Primary endpoint was the combined assessment of safety and feasibility. Secondary endpoints were specific toxicities, prostate-specific antigen progression-free survival (PFS), overall survival (OS), and quality of life (QoL). RESULTS Ninety-one patients completed therapy and have had a median follow-up of 22.3 months. Among acute genitourinary toxicities, grade 1 cystitis rates were 34.1% (39.1% in A; 28.9% in B) and 17.6% grade 2 (21.7% in A; 13.3% in B). Seven patients (8%) required urinary catheterization during treatment due to urinary retention, 5 of whom were in arm A. Regarding acute gastrointestinal toxicities, 2 patients treated with protons developed grade 3 rectal fistulas. Grade 1 radiation proctitis occurred in 12.1% (13.0% in A; 11.1% in B) and grade 2 in 5.5% (8.7% in A; 2.2% in B). No statistically significant differences in toxicity profiles between arms were found. Reduced QoL was evident mainly in fatigue, pain, and urinary symptoms during therapy and 6 weeks thereafter. All European Organization for Research and Treatment of Cancer QLQ-C30 and -PR25 scores improved during follow-up. CONCLUSIONS Hypofractionated irradiation using either carbon ions or protons results in comparable acute toxicities and QoL parameters. We found that hypofractionated particle irradiation is feasible and may be safe. Due to the occurrence of gel in the rectal wall and the consecutive occurrence of 2 rectal fistulas, we stopped using the insertion of spacer gel. Longer follow-up is necessary for evaluation of PFS and OS. (Ion Prostate Irradiation (IPI); NCT01641185; ClinicalTrials.gov.).

Validation of an established prognostic score after re-irradiation of recurrent glioma

Abstract Background: Re-irradiation (Re-RT) is offered widely in clinical routine, and has been established as a key element in the treatment of recurrent gliomas. At our center, generally re-resection is performed widely by an experienced neurosurgical team. Thus, Re-RT mostly offered to patients with macroscopic residuals or irresectable lesions, is applied later compared to other centers. Therefore, we sought to validate the Combs Prognostic Score developed in 2012 using our independent patient cohort. Patients and methods: We included 199 patients treated from 2002 until April 2016 for recurrent glioma at the Department of Radiation Oncology at the Klinikum Rechts der Isar, Munich. Different concepts of Re-RT were applied. Results: Median follow-up after Re-RT was 2.5 months. Median overall survival (OS) after Re-RT was 7.9 months for WHO IV gliomas, 11.3 months for WHO III gliomas, and 13.6 months for low-grade gliomas (WHO I/II). Univariate analyses confirmed the prognostic factors primary histology (p = 0.001), age (p = 0.002), and time between primary radiotherapy and Re-RT (p < 0.001). We also tested Karnofsky Performance Score (KPS), gender, and neurological symptoms before Re-RT as well as planning target volume and found only KPS also significant at p < 0.001. Comparing the prognostic score groups, the outcome was highly statistically significant at p < 0.001. Conclusion: In our analysis, we validated the Combs Prognostic Score. Validation in this independent large patient cohort confirms the significance of the score for glioma recurrences. Thus, the role of the Combs Prognostic Score might be an essential component of future clinical decision making and patient stratification.

[Database supported electronic retrospective analyses in radiation oncology: establishing a workflow using the example of pancreatic cancer].

PURPOSE Especially in the field of radiation oncology, handling a large variety of voluminous datasets from various information systems in different documentation styles efficiently is crucial for patient care and research. To date, conducting retrospective clinical analyses is rather difficult and time consuming. With the example of patients with pancreatic cancer treated with radio-chemotherapy, we performed a therapy evaluation by using an analysis system connected with a documentation system. MATERIALS AND METHODS A total number of 783 patients have been documented into a professional, database-based documentation system. Information about radiation therapy, diagnostic images and dose distributions have been imported into the web-based system. RESULTS For 36 patients with disease progression after neoadjuvant chemoradiation, we designed and established an analysis workflow. After an automatic registration of the radiation plans with the follow-up images, the recurrence volumes are segmented manually. Based on these volumes the DVH (dose volume histogram) statistic is calculated, followed by the determination of the dose applied to the region of recurrence. All results are saved in the database and included in statistical calculations. CONCLUSION The main goal of using an automatic analysis tool is to reduce time and effort conducting clinical analyses, especially with large patient groups. We showed a first approach and use of some existing tools, however manual interaction is still necessary. Further steps need to be taken to enhance automation. Already, it has become apparent that the benefits of digital data management and analysis lie in the central storage of data and reusability of the results. Therefore, we intend to adapt the analysis system to other types of tumors in radiation oncology.

Use of Complementary and Alternative Medicine (CAM) as Part of the Oncological Treatment: Survey about Patients’ Attitude towards CAM in a University-Based Oncology Center in Germany

Introduction To understand if and which patients would be open-minded to Complementary and Alternative Medicine (CAM) use parallel to their oncological treatment. Moreover, we sought to determine which methods are most accepted and which are the primary motivators to use CAM. Methods We developed and anonymously conducted a questionnaire for patients in the oncology center (TU Munich). Questions focus on different CAM methods, previous experiences, and willingness to apply or use CAM when offered in a university-based setting. Results A total of 171 of 376 patients (37.4% women, 62.0% men, 0.6% unknown) participated. This corresponds to a return rate of 45%. Median age was 64 years (17–87 years). Of all participants, 15.2% used CAM during their oncological therapy; 32.7% have used it in the past. The majority (81.9%) was not using CAM during therapy; 55.5% have not used CAM in the past respectively. The analysis revealed a significant correlation between education and CAM use during therapy (r = 0.18; p = 0.02), and CAM use in the past (r = 0.17; p = 0.04). Of all patients using CAM during therapy, favored methods were food supplements (42.3%), vitamins/minerals (42.3%), massage (34.6%). Motivations are especially the reduction of side effect and stress, the positive effect of certain CAM-treatments on the immune system and tumor therapy. Results showed no difference between women and men. Most patients not having had any experience with CAM complain about the deficiency of information by their treating oncologist (31.4%) as well as missing treatment possibilities (54.3%). Conclusion Since many patients believe in study results demonstrating the efficacy of CAM, it stresses our task to develop innovative study protocols to investigate the outcomes of certain CAM on symptom reduction or other endpoints. Thus, prospective trials and innovative evidence-based treatment concepts to include CAM into high-end oncology is what patients demand and what a modern oncology center should offer.

mHealth and Application Technology Supporting Clinical Trials: Today’s Limitations and Future Perspective of smartRCTs

Nowadays, applications (apps) for smartphones and tablets have become indispensable especially for young generations. The estimated number of mobile devices will exceed 2.16 billion in 2016. Over 2.2 million apps are available in the Google Play store®, and about 1.8 million apps are available in the Apple App Store®. Google and Apple distribute nearly 70,000 apps each in the category Health and Fitness, and about 33,000 and 46,000 each in medical apps. It seems like the willingness to use mHealth apps is high and the intention to share data for health research is existing. This leads to one conclusion: the time for app-accompanied clinical trials (smartRCTs) has come. In this perspective article, we would like to point out the stones put in the way while trying to implement apps in clinical research. Further, we try to offer a glimpse of what the future of smartRCT research may hold.

Review of Developments in Electronic, Clinical Data Collection, and Documentation Systems over the Last Decade – Are We Ready for Big Data in Routine Health Care?

Recently, information availability has become more elaborate and widespread, and treatment decisions are based on a multitude of factors, including imaging, molecular or pathological markers, surgical results, and patient’s preference. In this context, the term “Big Data” evolved also in health care. The “hype” is heavily discussed in literature. In interdisciplinary medical specialties, such as radiation oncology, not only heterogeneous and voluminous amount of data must be evaluated but also spread in different styles across various information systems. Exactly this problem is also referred to in many ongoing discussions about Big Data – the “three V’s”: volume, velocity, and variety. We reviewed 895 articles extracted from the NCBI databases about current developments in electronic clinical data management systems and their further analysis or postprocessing procedures. Few articles show first ideas and ways to immediately make use of collected data, particularly imaging data. Many developments can be noticed in the field of clinical trial or analysis documentation, mobile devices for documentation, and genomics research. Using Big Data to advance medical research is definitely on the rise. Health care is perhaps the most comprehensive, important, and economically viable field of application.

Use of acupuncture to alleviate side effects in radiation oncology: Current evidence and future directions

Several reports have shown that acupuncture is an effective method of complementary medicine; however, only a few of these reports have focused on oncological patients treated with radiation therapy. Most of these studies discuss a benefit of acupuncture for side-effect reduction; however, not all could demonstrate significant improvements. Thus, innovative trial designs are necessary to confirm that acupuncture can alleviate side effects related to radiation therapy. In the present manuscript, we perform a broad review and discuss pitfalls and limitations of acupuncture in parallel with standard radiation therapy, which lead the way to novel treatment concepts.

Changes in Gross Tumor Volume and Organ Motion Analysis During Neoadjuvant Radiochemotherapy in Patients With Locally Advanced Pancreatic Cancer Using an In-House Analysis System.

Background and Purpose: During radiation treatment, movement of the target and organs at risks as well as tumor response can significantly influence dose distribution. This is highly relevant in patients with pancreatic cancer, where organs at risk lie in close proximity to the target. Material and Methods: Data sets of 10 patients with locally advanced pancreatic cancer were evaluated. Gross tumor volume deformation was analyzed. Dose changes to organs at risk were determined with focus on kidneys both without adaptive radiotherapy compensation and with replanning based on weekly acquired computed tomography scans. Results: During irradiation, gross tumor volume changes between 0% and 26% and moves within a radius of 5 to 16 mm. Required maximal dose to organs at risk for kidneys can be met with the current practice of matching computed tomography scans during treatment and adjusting patient position accordingly. Comparison of the mean doses and V15, V20 volumes demonstrated that weekly replanning could bring a significant dose sparing of the left kidney. Conclusion: Manual matching with focus on bony structures can lead to overall acceptable positioning of patients during treatment. Thus, tolerance doses of organs at risk, such as the kidneys, can be met. With adequate margins, normal tissue constraints to organs at risk can be kept as well. Adaptive radiotherapy approaches (in this case with weekly rescanning) reduced dose to organs at risk, which may be especially important for hypofractionated approaches.

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.

Editorial: Data Based Radiation Oncology—Design of Clinical Trials

1 Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany, 2 Institute for Innovative Radiotherapy (iRT), Helmholtz Zentrum München, Munich, Germany, 3 Department of Clinical Oncology, The University of Hong Kong Shenzhen Hospital, Shenzhen, China, 4 Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, The Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, MD, United States, 5 National Cancer Institute (NIH), Rockville, MD, United States