Radiotherapy Late Effects and Osteogenesis Imperfecta: Dos and Don’ts in Clinical Practice

In radiation oncology, little is known about possible difficulties in patients with Osteogenesis Imperfecta (OI). Because radiotherapy can cause various side-effects including bone, soft tissue and cardiovascular toxicities, we foresee that patients with OI may experience even more acute and late side-effects due to pre-existing problems. We present two cases of radiotherapy in patients with OI, measured the effects of radiation on their bone mineral density and provide clinical recommendations for patient tailored radiotherapy strategies in patients with OI

Automatic segmentation of organs at risk in thoracic CT scans by combining 2D and 3D convolutional neural networks

Segmentation of organs at risk (OARs) in medical images is an important step in treatment planning for patients undergoing radiotherapy (RT). Manual segmentation of OARs is often time-consuming and tedious. Therefore, we propose a method for automatic segmentation of OARs in thoracic RT treatment planning CT scans of patients diagnosed with lung, breast or esophageal cancer. The method consists of a combination of a 2D and a 3D convolutional neural network (CNN), where both networks have substantially different architectures. We analyse the performance for these networks individually and show that a combination of both networks produces the best results. With this combination, we achieve average Dice coefficients of 0.84± 0.05, 0.94± 0.02, 0.91± 0.02, and 0.93± 0.01 for the esophagus, heart, trachea, and aorta, respectively. These results demonstrate potential for automating segmentation of organs at risk in routine radiotherapy treatment planning

Changes in cortical thickness and volume after cranial radiation treatment : A systematic review

Cognitive decline has a clear impact on quality of life in patients who have received cranial radiation treatment. The pathophysiological process is most likely multifactorial, with a possible role for decreased cortical thickness and volume. As radiotherapy treatment systems are becoming more sophisticated, precise sparing of vulnerable regions and tissue is possible. This allows radiation oncologists to make treatment more patient-tailored. A systematic search was performed to collect and review all available evidence regarding the effect of cranial radiation treatment on cortical thickness and volume. We searched the Pubmed, Embase and Cochrane databases, with an additional reference check in the Scopus database. Studies that examined cortical changes on MRI within patients as well as between treated and non-treated patients were included. The quality of the studies was assessed with a checklist specially designed for this review. No meta-analysis was performed due to the lack of randomised trials. Out of 1915 publications twenty-one papers were selected, of which fifteen observed cortical changes after radiation therapy. Two papers reported radiation-dependent decrease in cortical thickness within patients one year after radiation treatment, suggesting a clear relation between the two. However, study quality was considered mostly suboptimal, and there was great inhomogeneity between the included studies. This means that, although there has been increasing interest in the effects of radiation treatment on cortex morphology, no reliable conclusion can be drawn based on the currently available evidence. This calls for more research, preferably with a sufficiently large patient population, and adequate methodology

Untangling the diffusion signal using the phasor transform

Separating the decay signal from diffusion-weighted scans into two or more components can be challenging. The phasor technique is well established in the field of optical microscopy for visualization and separation of fluorescent dyes with different lifetimes. The use of the phasor technique for separation of diffusion-weighted decay signals was recently proposed. In this study, we investigate the added value of this technique for fitting decay models and visualization of decay rates. Phasor visualization was performed in five glioblastoma patients. Using simulations, the influence of incorrect diffusivity values and of the number of b-values on fitting a three-component model with fixed diffusivities (dubbed “unmixing”) was investigated for both a phasor-based fit and a linear least squares (LLS) fit. Phasor-based intravoxel incoherent motion (IVIM) fitting was compared with nonlinear least squares (NLLS) and segmented fitting (SF) methods in terms of accuracy and precision. The distributions of the parameter estimates of simulated data were compared with those obtained in a healthy volunteer. In the phasor visualizations of two glioblastoma patients, a cluster of points was observed that was not seen in healthy volunteers. The identified cluster roughly corresponded to the enhanced edge region of the tumor of two glioblastoma patients visible on fluid-attenuated inversion recovery (FLAIR) images. For fitting decay models the usefulness of the phasor transform is less pronounced, but the additional knowledge gained from the geometrical configuration of phasor space can aid fitting routines. This has led to slightly improved fitting results for the IVIM model: phasor-based fitting yielded parameter maps with higher precision than the NLLS and SF methods for parameters f and D (interquartile range [IQR] for f: NLLS 27, SF 12, phasor 5.7%; IQR for D: NLLS 0.28, SF 0.18, phasor 0.10 μm2/s). For unmixing, LLS fitting slightly but consistently outperformed phasor-based fitting in all of the tested scenarios

Occurrence of an Abscopal Radiation Recall Phenomenon in a Glioblastoma Patient Treated with Nivolumab and Re-Irradiation

Glioblastoma multiforme is the most frequent primary brain tumor. The clinical course of glioblastoma is almost invariably fatal. Combined chemo-irradiation with temozolomide is currently the standard of care for newly diagnosed glioblastoma and concurrent Nivolumab, an anti-PD-1 monoclonal antibody is being studied for de novo glioblastoma. We present a 62-year old patient with glioblastoma, which was discovered during evaluation of sudden-onset moderate ataxia. Following craniotomy of the glial tumour he received chemo radiation. During this first-line treatment the patient participated in the CA209-548 phase III placebo controlled study investigating the addition of concurrent nivolumab. One month after the last administration of nivolumab after 60 weeks of study participation, magnetic resonance imaging scan showed progressive disease. Therefore stereotactic re-irradiation was given. Five days after completing radiation therapy and 50 days after his last nivolumab course he developed a mild diffuse generalized pruritic maculopapular exanthema. Skin biopsy was very indicative for a drug hypersensitivity reaction. The maculopapular rash and pruritus was successfully treated with moderate potency topical corticosteroids and prednisone. With the introduction of PD1/PD-L1 inhibitors and other immunotherapies tweaking the immune system to target cancer cells one can argue that once local radiation triggers a local immune mediated hypersensitivity reaction as seen in radiation recall dermatitis, the subsequent hypersensitivity reaction which would traditionally only be a local reaction is now possible to advance to more pronounced (systemic) reactions as seen in an abscopal effect. Therefore, we propose a combined name to coin this effect, the abscopal radiation recall phenomenon

The impact of schizophrenia spectrum disorder, bipolar disorder and borderline personality disorder on radiotherapy treatment and overall survival in cancer patients: A matched pair analysis

Introduction: The effect of a psychiatric disorder (PD) on the choice of radiotherapy regimens and subsequent cancer control outcomes is largely unknown. In this study, we evaluated differences in radiotherapy regimens and overall survival (OS) between cancer patients with a PD in comparison with a control population of patients without a PD. Methods: Referred patients with a PD (i.e. schizophrenia spectrum disorder, bipolar disorder or borderline personality disorder) were included through a text-based search of the electronic patient database of all the patients that received radiotherapy between 2015 and 2019 at a single centre. Each patient was matched to a patient without a PD. Matching was based on cancer type, staging, performance score (WHO/KPS), non-radiotherapeutic cancer treatment, gender and age. Outcomes were the amount of fractions received, total dose, and OS. Results: 88 patients with PD were identified; 44 patients with schizophrenia spectrum disorder, 34 with bipolar disorder, and 10 with borderline personality disorder. Matched patients without a PD showed similar baseline characteristics. No statistically significant difference was observed regarding the number of fractions with a median of 16 (interquartile range [IQR] 3–23) versus 16 (IQR 3–25), respectively (p = 0.47). Additionally, no difference in total dose was found. Kaplan-Meier curves showed a statistically significant difference in OS between the patients with a PD versus those without a PD, with 3-year OS rates of 47 % versus 61 %, respectively (hazard ratio 1.57, 95 % confidence interval 1.05–2.35, p = 0.03). No clear differences in causes of death were observed. Conclusion: Cancer patients referred for radiotherapy with schizophrenia spectrum disorder, bipolar disorder or borderline personality disorder receive similar radiotherapy schedules for a variety of tumour types but attain worse survival

Patterns of re-irradiation for recurrent gliomas and validation of a prognostic score

PURPOSE OR OBJECTIVE: Re-irradiation is a generally accepted method for salvage treatment in patients with recurrent glioma. However, no standard radiation regimen has been defined. This study aims to compare the efficacy and safety of different treatment regimens and to independently externally validate a recently published reirradiation risk score. MATERIAL AND METHODS: We retrospectively analyzed a cohort of patients with recurrent malignant glioma treated with salvage conventionally fractionated (CFRT), hypofractionated (HFRT) or stereotactic radiotherapy (SRT) between 2007 and 2017 at the University Medical Centers in Utrecht and Groningen. RESULTS: Of the 121 patients included, 60 patients (50%) underwent CFRT, 22 (18%) HFRT and 39 (32%) SRT. The primary tumor was grade II-III in 52 patients and grade IV in 69 patients with median Overall Survival (mOS) since first surgery of 113 [Interquartile range: 53.2-137] and 39.7 [24.6-64.9] months respectively (p < 0.01). Overall, mOS from the first day of re-irradiation was 9.7 months [6.5-14.6]. No significant difference in mOS was found between the treatment groups. In multivariate analysis, the Karnofsky performance scale ≥70% (p < 0.01), re-irradiation for first recurrence (p = 0.02), longer time interval between RT start dates (p < 0.01) and smaller planning target volume (p < 0.05) were significant favorable prognostic factors. The reirradiation risk score was validated. CONCLUSION: In our series, mOS after reirradiation was sufficient to justify use of this modality. Until a reliable treatment decision tool is developed based on larger retrospective research, the decision for re-irradiation schedule should remain personalized and based on a multidisciplinary evaluation of each patient

A Systematic Review of Devices and Techniques that Objectively Measure Patients' Pain

Background: Assessment of pain is important in daily clinical practice and as an endpoint in clinical studies. Because pain perception is highly subjective, pain measurement is complex. Selfrating pain scales are currently of great importance but have limitations. They depend on many more factors than pain, which could lead to an incorrect assessment of therapies or clinical studies. Therefore, there is need for valid, reliable, safe, and low-cost methods to determine and quantify patients’ pain more objectively. Objective: To provide an overview of devices and techniques that can be used to administer a pain stimulus with similar intensity as the endogenous pain experienced by the patient, in order to quantify and subsequently follow patients’ pain more objectively. Study Design: In this systematic review, articles from PubMed, EMBASE, Cochrane library and Scopus were reviewed for eligibility. Methods: Studies that described a device or technique that could be used to induce a variable, controlled, and measurable pain stimulus were included. Studies that made correlations with established pain scales or those who compared outcomes in multiple tests were selected to assess validity and reliability. Results: A total of 1,308 manuscripts were initially retrieved. After independent screening by a team of 4 reviewers, 19 studies were eventually included describing 15 different devices or techniques. These devices could be divided into groups based on stimulus administration: electrical, external pressure (probe) and miscellaneous pain stimulators. Electrical stimulators were found to be tested extensively and proven to be both valid and reliable. Limitations: To correlate new techniques with older methods such as the Numeric Rating Scale (NRS) and Visual Analogue Scale (VAS) for which an improvement is desired, is debatable. To (partially) address this problem, the reliability is added as an additional primary outcome to assess which device works best. Further limitations include the heterogeneity of studies found in both the types of pain measured as in outcome measures presented. In addition, it is important to note that part of the devices described cannot directly be used for clinical practice due to products that have cease to exist or the description of solely techniques rather than testing ready-to-use devices. Conclusion: Several devices and techniques compared pain intensity experienced by patients with an external pain stimulus that potentially could be used as a new objective pain measurement tool. Given the results of our review, electrical stimulators that have been tested extensively with high validity, reliability, and feasibility would be recommended for use for clinical and research purposes. Moreover, normalization of pain intensity scores for current perception is important. Pain intensity normalization leads to higher correlations with established pain scales and possibly to increased inter-patient reliability

MR-Only Brain Radiation Therapy : Dosimetric Evaluation of Synthetic CTs Generated by a Dilated Convolutional Neural Network

Purpose: This work aims to facilitate a fast magnetic resonance (MR)-only workflow for radiation therapy of intracranial tumors. Here, we evaluate whether synthetic computed tomography (sCT) images generated with a dilated convolutional neural network (CNN) enable accurate MR-based dose calculations in the brain. Methods and Materials: We conducted a retrospective study of 52 patients with brain tumors who underwent both computed tomography (CT) and MR imaging for radiation therapy treatment planning. To generate the sCTs, a T1-weighted gradient echo MR sequence was selected from the clinical protocol for multiple types of brain tumors. sCTs were created for all 52 patients with a dilated CNN using 2-fold cross validation; in each fold, 26 patients were used for training and the remaining 26 patients were used for evaluation. For each patient, the clinical CT-based treatment plan was recalculated on sCT. We calculated dose differences and gamma pass rates between CT- and sCT-based plans inside body and planning target volume. Geometric fidelity of the sCT and differences in beam depth and equivalent path length were assessed between both treatment plans. Results: sCT generation took 1 minute per patient. Over the patient population, the mean absolute error of the sCT within the intersection of body contours was 67 ± 11 HU (±1 standard deviation [SD], range: 51-117 HU), and the mean error was 13 ± 9 HU (±1 SD, range: –2 to 38 HU). Dosimetric analysis showed mean deviations of 0.00% ± 0.02% (±1 SD, range: –0.05 to 0.03) for dose within the body contours and –0.13% ± 0.39% (±1 SD, range: –1.43 to 0.80) inside the planning target volume. Mean γ1mm/1% was 98.8% ± 2.2% for doses >50% of the prescribed dose. Conclusions: The presented dilated CNN generated sCTs from conventional MR images without adding scan time to the acquisition. Dosimetric evaluation suggests that dose calculations performed on the sCTs are accurate and can therefore be used for MR-only intracranial radiation therapy treatment planning