In vivodosimetry in cancer patients undergoing intraoperative radiation therapy.

In vivodosimetry (IVD) is an important tool in external beam radiotherapy (EBRT) to detect major errors by assessing differences between expected and delivered dose and to record the received dose by individual patients. Also, in intraoperative radiation therapy (IORT), IVD is highly relevant to register the delivered dose. This is especially relevant in low-risk breast cancer patients since a high dose of IORT is delivered in a single fraction. In contrast to EBRT, online treatment planning based on intraoperative imaging is only under development for IORT. Up to date, two commercial treatment planning systems proposed intraoperative ultrasound or in-room cone-beam CT for real-time IORT planning. This makes IVD even more important because of the possibility for real-time treatment adaptation. Here, we summarize recent developments and applications of IVD methods for IORT in clinical practice, highlighting important contributions and identifying specific challenges such as a treatment planning system for IORT. HDR brachytherapy as a delivery technique was not considered. We add IVD for ultrahigh dose rate (FLASH) radiotherapy that promises to improve the treatment efficacy, when compared to conventional radiotherapy by limiting the rate of toxicity while maintaining similar tumour control probabilities. To date, FLASH IORT is not yet in clinical use.

Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review.

OBJECTIVE: To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs). DESIGN AND METHODS: We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy. RESULTS: Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population. CONCLUSION: ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.

The level of reporting of neurocognitive outcomes in randomised controlled trials of brain tumour patients: A systematic review.

BACKGROUND: Neurocognitive impairment is frequently present in brain tumour patients and is therefore considered an important outcome in brain tumour research. To use neurocognitive outcomes (NCO) in clinical decision-making, neurocognitive evidence should be of sufficiently high quality. We aimed to investigate the level of neurocognitive functioning reporting in randomised controlled trials (RCTs) in brain tumour patients. METHODS: We conducted a systematic literature search in several databases up to August 2017. Of the selected relevant RCTs, the following data were retrieved: basic trial demographics and NCO characteristics, quality of NCO reporting and risk of bias. We also analysed studies that should impact clinical decision-making based on their quality of reporting. RESULTS: We identified 65 RCTs, of which NCO was the primary end-point in 14 (22%). Important methodological limitations were related to the documentation of statistical approaches for dealing with missing data and to discussing limitations and generalisability issues uniquely related to the NCO components. Risk of bias was high regarding blinding of personnel and incomplete outcome data. Twenty RCTs (31%), eight with NCO as primary end-point and 12 as secondary end-point, satisfied a sufficient number of criteria to be classified as 'high-quality' NCO evidence. Most of these studies did contribute to clinical decision-making. CONCLUSION: Investigators involved in brain tumour research should give attention to methodological challenges related to NCO reporting as identified in this review, as 'high-quality' reporting of NCO evidence can be of value in clinical decision-making.

Prevalence of changes in personality and behavior in adult glioma patients: a systematic review.

BACKGROUND: Gliomas are rare, with a dismal outcome and an obvious impact on quality of life, because of neurological, physical and cognitive problems, as well as personality and behavioral changes. These latter changes may affect the lives of both patients and their relatives in a profound way, but it is unclear how often this occurs and to what extent. METHODS: We performed a systematic review to determine the prevalence of changes in personality and behavior in glioma patients. Searches were conducted in PubMed/Medline, PsycINFO, Cochrane, CINAHL and Embase. Based on predetermined in- and exclusion criteria, papers were screened for eligibility. Information on the topics of interest were extracted from the full-text papers. RESULTS: The search yielded 9895 papers, of which 18 were found to be eligible; 9 qualitative and 9 quantitative studies. The reported prevalence rates of changes in personality and/or behavior varied from 8%-67% in glioma patients, and was 100% in a case series with bilateral gliomas. Moreover, these changes were associated with distress and a lower quality of life of patients as well as informal caregivers. Methods of measurement of personality and behavioral changes differed considerably, as did the description of these changes. CONCLUSION: To determine the true prevalence of changes in behavior and personality, present but poorly labeled in the reported studies, prospective studies are needed using proper definitions of personality and behavioral changes and validated measurement tools. Ultimately, these findings may result in improved supportive care of both patients and caregivers, during the disease trajectory.

Dose-effect relation in stereotactic radiotherapy for brain metastases. A systematic review.

PURPOSE: Stereotactic radiotherapy (SRT) of brain metastases is considered effective when long-term local control is obtained. However, dose-effect data are scarce. We, therefore, performed a systematic literature search to assess the evidence concerning the relation of SRT dose and local control probability. METHODS AND MATERIALS: A search was performed for papers describing patients treated with SRT for brain metastases, published from 1990 through 2009, in the electronic databases Medline (Pubmed) and Embase. We selected only papers reporting actuarial local control probability, in which a fixed dose had been prescribed and in which the size of the metastases was given. Series with SRT as a boost after whole brain irradiation (WBI) or with SRT after surgery were excluded. From the selected papers we extracted data on dose, local control rates and necrosis rates. Biological effective doses of the linear-quadratic-cubic model, using an α/ß of 12Gy (BED(12)), were calculated and a dose-response curve was constructed. RESULTS: Eleven papers fulfilled the selection criteria for further analysis. Six-month local control rates were higher than 80% in almost all the series irrespective of dose. Twelve-month local control rates, however, varied and were higher than 80%, higher than 60% and lower than 50% with single doses of ≥21Gy, ≥18Gy and ≤15Gy, respectively, and 70% or higher with fractionated SRT (FSRT). A BED(12) of at least 40Gy was associated with a twelve-month local control rate of 70% or more. CONCLUSION: Local control after single fraction SRT is highly dependent upon dose and is high (>80%) after 21Gy or more, but low (<50%) after 15Gy or less. We conclude that SRT for brain metastases should preferably be applied with a BED(12) of at least 40Gy corresponding with a single fraction of 20Gy, two fractions of 11.6Gy or three fractions of 8.5Gy.