Risk assessment, surveillance, and nonpharmaceutical prevention of acute radiation dermatitis: results of a multicentric survey among the German-speaking radiation oncology community.

PURPOSE: Radiation dermatitis (RD) represents one of the most frequent side effects in radiotherapy (RT). Despite technical progress, mild and moderate RD still affects major subsets of patients and identification and management of patients with a high risk of severe RD is essential. We sought to characterize surveillance and nonpharmaceutical preventive management of RD in German-speaking hospitals and private centers. METHODS: We conducted a survey on RD among German-speaking radiation oncologists inquiring for their evaluation of risk factors, assessment methods, and nonpharmaceutical preventive management of RD. RESULTS: A total of 244 health professionals from public and private institutions in Germany, Austria, and Switzerland participated in the survey. RT-dependent factors were deemed most relevant for RD onset followed by lifestyle factors, emphasizing the impact of treatment conceptualization and patient education. While a broad majority of 92.8% assess RD at least once during RT, 59.0% of participants report RD at least partially arbitrarily and 17.4% stated to classify RD severity solely arbitrarily. 83.7% of all participants were unaware of patient-reported outcomes (PROs). Consensus exists on some lifestyle recommendations like avoidance of sun exposure (98.7%), hot baths (95.1%), and mechanical irritation (91.8%) under RT, while deodorant use (63.4% not at all, 22.1% with restrictions) or application of skin lotion (15.1% disapproval) remain controversial and are not recommended by guidelines or evidence-based practices. CONCLUSION: Identification of patients at an increased risk of RD and subsequent implementation of adequate preventive measures remain relevant and challenging aspects of clinical routines. Consensus exists on several risk factors and nonpharmaceutical prevention recommendations, while RT-dependent risk factors, e.g., the fractionation scheme, or hygienic measures like deodorant use remain controversial. Surveillance is widely lacking methodology and objectivity. Intensifying outreach in the radiation oncology community is needed to improve practice patterns.

The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials.

OBJECTIVE: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. METHODS: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. RESULTS: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). CONCLUSION: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small.

Clinical trial design for local therapies for brain metastases: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group.

The goals of therapeutic and biomarker development form the foundation of clinical trial design, and change considerably from early-phase to late-phase trials. From these goals, decisions on specific clinical trial design elements, such as endpoint selection and statistical approaches, are formed. Whereas early-phase trials might focus on finding a therapeutic signal to make decisions on further development, late-phase trials focus on the confirmation of therapeutic impact by considering clinically meaningful endpoints. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we highlight issues related to, and provide recommendations for, the design of clinical trials on local therapies for CNS metastases from solid tumours. We discuss endpoint selection criteria, the analysis appropriate for early-phase and late-phase trials, the association between tumour-specific and clinically meaningful endpoints, and possible issues related to the estimation of local control in the context of competing risks. In light of these discussions, we make specific recommendations on the clinical trial design of local therapies for brain metastases.

Response assessment criteria for brain metastases: proposal from the RANO group.

CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials.

Follow-up assessment of vestibular schwannomas: volume quantification versus two-dimensional measurements.

INTRODUCTION: A conservative treatment strategy is often proposed as a primary treatment option in the management of vestibular schwannomas (VS). In this "wait and scan" policy, audiovestibular symptoms are monitored regularly, and VS growth is measured on consecutive magnetic resonance images (MRI). The aim of this study is validation of two-dimensional versus volume MRI assessment in the longitudinal follow-up of VS and to define tumor growth beyond measurement error. METHODS: MRI scans of 68 consecutive patients with VS were analyzed retrospectively. Two-dimensional and volume measurements on contrast enhanced (CE) T1- and T2-weighted images were performed independently by two readers. Smallest detectable differences (SDD) were calculated, and intraclass correlation coefficients (ICCs) were determined for both assessment methods. RESULTS: Two-dimensional and volume measurements both showed best reproducibility on CE T1-weighted images. SDD for differences relative to baseline MRI [SDD (%)] for two-dimensional measurements had a higher interobserver error compared to volume measurements (40% versus 19.7%), which decreases when tumor size increases. The ICC for two-dimensional measurements in three directions was 0.947, 0.974, and 0.978 and for volume measurements 0.999. CONCLUSION: Volume measurements are more accurate compared to two-dimensional measurements for the evaluation of VS growth. These measurements are assessed preferably on CE T1-weighted images. SDD (%) strongly depends on VS size. SDD between consecutive scans exceeds the common clinical applied criterion of 1 or 2 mm growth to define growth.

Repositioning accuracy of fractionated stereotactic irradiation: assessment of isocentre alignment for different dental fixations by using sequential CT scanning.

BACKGROUND AND PURPOSE: To quantify the accuracy and reproducibility of patient repositioning in fractionated stereotactic conformal radiotherapy (SCRT) using dental fixations in conjunction with a stereotactic head mask. PATIENTS AND METHODS: One hundred and fourteen verification CT scans were performed on 57 patients in order to check set-up alignment. The first scan was done immediately after the first treatment. Twelve patients were checked for alignment accuracy with weekly CT scans over a period of 3-6 weeks, all others had 1-2 scans. Two different dental fixations were used in combination with a non-invasive mask system: an upper jaw support (35 patients) and a customised bite-block (17 patients). Five patients were treated with no additional fixation. Co-registration to the planning CT was used to assess alignment of the isocentre to the reference markers. Additionally, the intra-operator variability of image co-registration was assessed. RESULTS: There was a significant improvement of the overall alignment in using the bite-block instead of the upper jaw support (P<0.001). The mean deviation was for the bite-block 2.2+/-1.1 mm (1 SD), for the upper jaw support 3.3+/-1.8 mm and 3.7+/-2.8 mm for the mask alone. Overall isocentre deviations independent of the method of fixation were 2.8 mm (1.7 mm, 1 SD). Displacements in CC direction were significantly less for the bite-block compared to the upper jaw support (P=0.03). The addition of an upper jaw support significantly reduced lateral rotations compared to the mask system alone (P=0.03). The intra-operator variability of image co-registration was 1.59+/-0.49 mm (1 SD). CONCLUSION: The reproducibility of patient positioning using a re-locatable head mask system combined with a bite-block is within the reported range for similar devices and is preferable to a simple upper jaw support. In order to further reduce the margin for the planning target volume an intra-oral dental fixation is recommended.