Proton arc therapy increases the benefit of proton therapy for oropharyngeal cancer patients in the model based clinic

Background and purpose: In the model-based approach, patients qualify for proton therapy when the reduction in risk of toxicity (ΔNTCP) obtained with IMPT relative to VMAT is larger than predefined thresholds as defined by the Dutch National Indication Protocol (NIPP). Proton arc therapy (PAT) is an emerging technology which has the potential to further decrease NTCPs compared to IMPT. The aim of this study was to investigate the potential impact of PAT on the number of oropharyngeal cancer (OPC) patients that qualify for proton therapy.Materials and methods: A prospective cohort of 223 OPC patients subjected to the model-based selection procedure was investigated. 33 (15%) patients were considered unsuitable for proton treatment before plan comparison. When IMPT was compared to VMAT for the remaining 190 patients, 148 (66%) patients qualified for protons and 42 (19%) patients did not. For these 42 patients treated with VMAT, robust PAT plans were generated.Results: PAT plans provided better or similar target coverage compared to IMPT plans. In the PAT plans, integral dose was significantly reduced by 18% relative to IMPT plans and by 54% relative to VMAT plans. PAT decreased the mean dose to numerous organs-at-risk (OARs), further reducing NTCPs. The ΔNTCP for PAT relative to VMAT passed the NIPP thresholds for 32 out of the 42 patients treated with VMAT, resulting in 180 patients (81%) of the complete cohort qualifying for protons.Conclusion: PAT outperforms IMPT and VMAT, leading to a further reduction of NTCP-values and higher ΔNTCP-values, significantly increasing the percentage of OPC patients selected for proton therapy.</p

Liver Resection for Hepatic Metastases from Soft Tissue Sarcoma:A Nationwide Study

Contains fulltext : 209467pub.pdf (publisher's version ) (Open Access

Cumulative Corticosteroid Sparing Effect of Anti-Interleukin-5/5Ra In Eosinophilic Asthma

BACKGROUND: Anti-interleukin (IL)-5/IL-5 receptor α (IL-5Ra) therapy has been shown to reduce maintenance oral corticosteroid (OCS) dose in severe eosinophilic asthma. However, the effect on cumulative OCS exposure is currently unknown. Neither is it known how prior OCS exposure affects response to anti-IL-5/5Ra treatment. We aimed primarily to compare the cumulative OCS exposure over a 2-year period before and after anti-IL-5/5Ra initiation, and secondarily to investigate whether duration and cumulative OCS exposure prior to anti-IL-5/5Ra influence the ability to discontinue OCS within 2 years of anti-IL-5/5Ra therapy. METHODS: This real-world nationwide observational registry-based study evaluated all dispensed OCS from 389 adults with severe eosinophilic asthma included in the Dutch Severe Asthma Registry (RAPSODI) 2 years before and 2 years after initiating anti-IL-5/5Ra. The Wilcoxon signed-rank test and multivariable regression analyses were used. RESULTS: Median (interquartile range) cumulative OCS exposure in the 2 years before and after anti-IL-5/5Ra initiation decreased from 2.715 (1.150–5.539) to 1.050 (0.300–3.640) g (p<0.001). 52% of patients were able to discontinue OCS within 2 years after anti-IL-5/5Ra therapy, which was independently predicted by lower and shorter prior OCS exposure. CONCLUSIONS: This real-world study showed that anti-IL-5/5Ra therapy leads to a significant reduction in cumulative OCS exposure over a 2-year period. Patients with lower and shorter OCS exposure were more likely to completely eliminate OCS. Since cumulative exposure increased progressively prior to anti-IL-5/5Ra initiation, our data suggest that early intervention leads to a better long-term prognosis in patients with severe eosinophilic asthma

The type I interferon signature in leukocyte subsets from peripheral blood of patients with early arthritis: a major contribution by granulocytes

The type I interferon (IFN) signature in rheumatoid arthritis (RA) has shown clinical relevance in relation to disease onset and therapeutic response. Identification of the cell type(s) contributing to this IFN signature could provide insight into the signature's functional consequences. The aim of this study was to investigate the contribution of peripheral leukocyte subsets to the IFN signature in early arthritis. Blood was collected from 26 patients with early arthritis and lysed directly or separated into peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs). PBMCs were sorted into CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes by flow cytometry. Messenger RNA expression of three interferon response genes (IRGs RSAD2, IFI44L, and MX1) and type I interferon receptors (IFNAR1 and IFNAR2) was determined in whole blood and blood cell subsets by quantitative polymerase chain reaction. IRG expression was averaged to calculate an IFN score for each sample. Patients were designated "IFN(high)" (n = 8) or "IFN(low)" (n = 18) on the basis of an IFN score cutoff in whole peripheral blood from healthy control subjects. The difference in IFN score between IFN(high) and IFN(low) patients was remarkably large for the PMN fraction (mean 25-fold) compared with the other subsets (mean 6- to 9-fold), indicating that PMNs are the main inducers of IRGs. Moreover, the relative contribution of the PMN fraction to the whole-blood IFN score was threefold higher than expected from its abundance in blood (p = 0.008), whereas it was three- to sixfold lower for the other subsets (p ≤ 0.063), implying that the PMNs are most sensitive to IFN signaling. Concordantly, IFNAR1 and IFNAR2 were upregulated compared with healthy controls selectively in patient PMNs (p ≤ 0.0077) but not in PBMCs. PMNs are the main contributors to the whole-blood type I IFN signature in patients with early arthritis, which seems due to increased sensitivity of these cells to type I IFN signaling. Considering the well-established role of neutrophils in the pathology of arthritis, this suggests a role of type I IFN activity in the disease as wel

Imaging of pediatric great vessel stents: Computed tomography or magnetic resonance imaging?

__Background:__ Complications might occur after great vessel stent implantation in children. Therefore follow- up using imaging is warranted. __Purpose:__ To determine the optimal imaging modality for the assessment of stents used to treat great vessel obstructions in children. __Material and methods:__ Five different large vessel stents were evaluated in an in-vitro setting. All stents were expanded to the maximal vendor recommended diameter (20mm; n = 4 or 10mm; n = 1), placed in an anthropomorphic chest phantom and imaged with a 256-slice CT-scanner. MRI images were acquired at 1.5T using a multi-slice T2-weighted turbo spin echo, an RFspoiled three-dimensional T1-weighted Fast Field Echo and a balanced turbo field echo 3D seq

Cognitive Impairment in Long-Term Survivors of Testicular Cancer More Than 20 Years after Treatment

SIMPLE SUMMARY: Impaired cognition can be a late effect after treatment in long-term testicular cancer survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very-long-term survivors after treatment. In this study, we enrolled testicular cancer survivors with a follow-up duration ≥ 20 years—and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular damage and aging parameters. We included 184 testicular cancer survivors (66 chemotherapy patients, 53 radiotherapy patients, and 65 orchiectomy only patients) and 70 healthy controls. The median follow-up was 26 years. Testicular cancer survivors performed worse on cognitive tests compared to controls. In univariate analysis, the presence of hypogonadism was associated with lower cognitive scores. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. ABSTRACT: Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls. Methods: In this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)—with a follow-up duration ≥ 20 years—and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs). Results: We included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20–42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score −0.85; 95% CI −1.39 to −0.33) compared to controls (mean 0.67; 95% CI −0.21 to 1.57, p < 0.01). In univariate analysis, the presence of hypogonadism (β −1.50, p < 0.01), high c-PWV (β −0.35, p = 0.09), and high AGEs (β −1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (β −1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p < 0.01). Conclusions: Long-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. Trial Registration: NCT02572934

The tubarial salivary glands:A potential new organ at risk for radiotherapy

Introduction: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy. Materials and methods: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated. Results: All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated posttreatment xerostomia and dysphagia >= grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p =.007; 0.016/gy, 95%CI 0.001-0.031, p =.036). Follow-up at 24 months had similar results. Conclusion: The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life. (C) 2020 The Authors. Published by Elsevier B.V

Outcome of Reverse Switching From CT-P13 to Originator Infliximab in Patients With Inflammatory Bowel Disease

BACKGROUND: Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are "reverse switched" to treatment with the originator. Here we assess the prevalence of reverse switching, including its indication and outcomes. METHODS: In this retrospective multicenter cohort study, data on patients with IBD from 9 hospitals in the Netherlands were collected. All adult patients with IBD were included if they previously had been switched from originator infliximab to the biosimilar CT-P13 and had a follow-up time of at least 52 weeks after the initial switch. The reasons for reverse switching were categorized into worsening gastrointestinal symptoms, adverse effects, or loss of response to CT-P13. Drug persistence was analyzed through survival analyses. RESULTS: A total of 758 patients with IBD were identified. Reverse switching was observed in 75 patients (9.9%). Patients with reverse switching were predominantly female (70.7%). Gastrointestinal symptoms (25.5%) and dermatological symptoms (21.8%) were the most commonly reported reasons for reverse switching. In 9 patients (12.0%), loss of response to CT-P13 was the reason for reverse switching. Improvement of reported symptoms was seen in 73.3% of patients after reverse switching and 7 out of 9 patients (77.8%) with loss of response regained response. Infliximab persistence was equal between patients who were reverse-switched and those who were maintained on CT-P13. CONCLUSIONS: Reverse switching occurred in 9.9% of patients, predominantly for biosimilar-attributed adverse effects. Switching back to originator infliximab seems effective in patients who experience adverse effects, worsening gastrointestinal symptoms, or loss of response after switching from originator infliximab to CT-P13

Low preoperative skeletal muscle density is predictive for negative postoperative outcomes in older women with ovarian cancer

Objective. To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer.Methods. A multicenter, retrospective cohort study was performed in women >= 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3. Low skeletal muscle mass was defined as skeletal muscle index = 2).Conclusion. Low skeletal muscle density, as a proxy of muscle quality, is associated with poor postoperative outcomes in older patients with advanced stage ovarian cancer. These findings can contribute to postoperative risk assessment and clinical decision making. (C) 2021 The Author(s). Published by Elsevier Inc.Cervix cance