Impressive thrombocytosis evolving in a patient with a BCR-ABL positive CML in major molecular response during dasatinib treatment unmasks an additional JAK2V617F.

We present a case of a 42-year old female with the rare diagnosis of a myeloproliferative syndrome harboring both a BCR-ABL transclocation and a JAK2V617F mutation.Initially diagnosed with a CML, the patient underwent treatment with imatinib followed by dasatinib. Despite a major molecular response, the patient developed a thrombocytosis. Molecular analyses revealed a heterozygous JAK2V617F mutation, which was detected retrospectively in the bone marrow at the time of CML diagnosis.This case underlines the complexity of MPS pathogenesis. For the clinician, a JAK2 mutational screening should be performed in CML patients without hematological response in the absence of BCR-ABL

Impressive thrombocytosis evolving in a patient with a BCR-ABL positive CML in major molecular response during dasatinib treatment unmasks an additional JAK2V617F.

We present a case of a 42-year old female with the rare diagnosis of a myeloproliferative syndrome harboring both a BCR-ABL transclocation and a JAK2V617F mutation.Initially diagnosed with a CML, the patient underwent treatment with imatinib followed by dasatinib. Despite a major molecular response, the patient developed a thrombocytosis. Molecular analyses revealed a heterozygous JAK2V617F mutation, which was detected retrospectively in the bone marrow at the time of CML diagnosis.This case underlines the complexity of MPS pathogenesis. For the clinician, a JAK2 mutational screening should be performed in CML patients without hematological response in the absence of BCR-ABL

Neural correlates of working memory and its association with metabolic parameters in early-treated adults with phenylketonuria.

BACKGROUND Phenylketonuria (PKU) is an inborn error of metabolism affecting the conversion of phenylalanine (Phe) into tyrosine. Previous research has found cognitive and functional brain alterations in individuals with PKU even if treated early. However, little is known about working memory processing and its association with task performance and metabolic parameters. The aim of the present study was to examine neural correlates of working memory and its association with metabolic parameters in early-treated adults with PKU. METHODS This cross-sectional study included 20 early-treated adults with PKU (mean age: 31.4 years ± 9.0) and 40 healthy controls with comparable age, sex, and education (mean age: 29.8 years ± 8.2). All participants underwent functional magnetic resonance imaging (fMRI) of working memory to evaluate the fronto-parietal working memory network. Fasting blood samples were collected from the individuals with PKU to acquire a concurrent plasma amino acid profile, and retrospective Phe concentrations were obtained to estimate an index of dietary control. RESULTS On a cognitive level, early-treated adults with PKU displayed significantly lower accuracy but comparable reaction time in the working memory task compared to the control group. Whole-brain analyses did not reveal differences in working memory-related neural activation between the groups. Exploratory region-of-interest (ROI) analyses indicated reduced neural activation in the left and right middle frontal gyri and the right superior frontal gyrus in the PKU group compared to the control group. However, none of the ROI analyses survived correction for multiple comparisons. Neural activation was related to concurrent Phe, tyrosine, and tryptophan concentrations but not to retrospective Phe concentrations. CONCLUSION In early-treated adults with PKU, cognitive performance and neural activation are slightly altered, a result that is partly related to metabolic parameters. This study offers a rare insight into the complex interplay between metabolic parameters, neural activation, and cognitive performance in a sample of individuals with PKU

Prospective assessment of stress and health concerns of radiation oncology staff during the COVID-19 pandemic

Introduction and background The COVID-19 pandemic has required rapid and repetitive adjustment of radiotherapy practice, hospital-level and department-level organization and hygiene measures. To prospectively monitor and manage stress levels and health concerns, employees of a radiation oncology department were invited to participate in weekly online surveys during the first year of the pandemic. Materials and methods Starting March 31st, 2020, cross-sectional online surveys were distributed to all employees of the Department of Radiation Oncology, University Hospital Zurich. The survey included questions about the profession, the work setting, the global stress level as well as the health concerns during the past work week. Stress levels and health concerns were assessed on a 10-point scale. SurveyMonkey® was used to conduct the survey. Distribution was performed via email. Participation was anonymous and voluntary. Results Between March 2020 and February 2021, 50 weekly surveys were distributed to 127 employees on average and resulted in 1,877 individual responses. The average response rate was 30%. The mean global stress level varied significantly by profession, ranging from 2.7 (±2.5) points for administrative staff to 6.9 (±2.3) points for radiation therapy technicians (p < 0.001). The mean global stress level was highest with 4.8 (±2.9) points for in-hospital work with direct patient contact. Health concerns were highest regarding family and friends with 4.0 (±3.1) points on average. Changes of the stress level varied in correlation with infection waves. Conclusion Weekly online surveys for prospective assessment of stress levels and health concerns were successfully conducted during the first year of the COVID-19 pandemic, indicating their feasibility and value to monitor profession and workplace specific stress patterns and to allowed for tailored interventions. The physical and mental health of frontline healthcare workers in radiation oncology should remain a top priority for departmental leadership beyond the COVID-19 pandemic

Repeat stereotactic body radiotherapy for oligometastatic disease

BACKGROUND Patients with oligometastatic disease (OMD) treated with metastasis-directed definitive local therapy such as stereotactic body radiotherapy (SBRT) are at risk of developing new metastases. Here, we compare characteristics and outcomes of patients treated with a single course and repeat SBRT. MATERIALS/METHODS OMD patients treated with SBRT to 1-5 metastases were included in this retrospective study, and classified as single course or repeat SBRT. Progression-free survival (PFS), widespread failure-free survival (WFFS), overall survival (OS), systemic therapy-free survival (STFS) and cumulative incidence of different first failures were analyzed. Patient and treatment characteristics predicting the use of repeat SBRT were investigated using univariable and multivariable logistic regression. RESULTS Among the 385 patients included, 129 and 256 received repeat or single course SBRT, respectively. The most common primary tumor and OMD state in both groups were lung cancer and metachronous oligorecurrence. Patients treated with repeat SBRT had shorter PFS (p < 0.0001), while WFFS (p = 0.47) and STFS (p = 0.22) were comparable. Distant failure, particularly with a single metastasis, was more frequently observed in repeat SBRT patients. Repeat SBRT patients had longer median OS (p = 0.01). On multivariable logistic regression, low distant metastases velocity and more previous lines of systemic therapy significantly predicted the use of repeat SBRT. CONCLUSION Despite shorter PFS and comparable WFFS and STFS, repeat SBRT patients had longer OS. The role of repeat SBRT for OMD patients warrants further prospective investigation, focussing on predictive factors to select patients that might derive a benefit

Efficacy and safety analysis in metastatic cancer patients treated with multiple courses of repeat radiation therapy

BACKGROUND AND PURPOSE: Due to advances in oncology, a growing proportion of patients is treated with repetitive courses of radiotherapy. The aim of this study is to analyze whether radiotherapy maintains its safety and efficacy profile in patients treated with multiple repeat courses of irradiation. MATERIAL AND METHODS: All patients treated between 2011 and 2019 at our institution were screened for a minimum of five repeat irradiation courses, to analyze treatment characteristics, survival, safety and efficacy. The type of re-irradiation was classified according to ESTRO-EORTC consensus guidelines. RESULTS: A total of n = 112 patients receiving n = 660 radiotherapy courses were included in this retrospective cohort study. The most frequent primary tumors were lung cancer in 41.9 % (n = 47) and malignant melanoma in 8.9 % (n = 10). The most frequent re-irradiation types were repeat irradiation and Type 2 re-irradiation in 309 (46.8 %) and 113 (17.1 %) cases, respectively. Median survival after the first course of radiotherapy was 3.6 (0.3-13.4) years. Response to radiotherapy was observed in 548 (83.0 %) cases and CTCAE toxicity grade ≥ 3 was observed in 21 (3.2 %) cases. An increasing number of RT courses (HR: 1.30, p=<0.0001), Type 1 re-irradiation (HR 3.50, p = 0.008) and KPS ≤ 80 % (HR: 2.02, p = 0.002) were associated with significantly worse treatment responses. Toxicity rates remained stable with increasing numbers of RT courses. CONCLUSION: Multiple courses of repeat radiotherapy maintain a favorable therapeutic ratio of high response combined with reasonable safety profile

Evaluation of the prognostic value of the ESTRO EORTC classification of oligometastatic disease in patients treated with stereotactic body radiotherapy: A retrospective single center study

PURPOSE To explore the prognostic value of the oligometastatic disease (OMD) states as proposed by the European Society for Radiotherapy and Oncology (ESTRO) European Organisation for Research and Treatment of Cancer (EORTC) classification system. MATERIALS AND METHODS This retrospective single-institution study included patients with 1-5 extracranial metastases from any solid malignancy treated with SBRT to all metastases. OMD states were defined according to the ESTRO EORTC classification. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Discriminatory strength of the classification was assessed by Gönen & Heller's concordance probability estimate (CPE). Univariable and multivariable Cox regression models were used to assess predictors of OS and PFS. RESULTS In total, 385 patients were included. The median follow-up was 24.1 months. The most frequent OMD states were metachronous oligorecurrence (23.6%) and induced oligoprogression (18.7%). Induced OMD patients had significantly shorter median OS (28.1 months) compared with de-novo (46.3 months, p=0.002) and repeat OMD (50.3 months, p=0.002). Median PFS in de-novo OMD patients (8.8 months) was significantly longer than in repeat (5.4 months, p=0.002) and induced OMD patients (4.3 months, p<0.001). The classification system had moderate discriminatory strength for OS and PFS. Multivariable analyses confirmed that compared with induced OMD, de-novo was associated with longer PFS and repeat with longer OS. CONCLUSION All patients were successfully categorized according to the ESTRO EORTC classification system. The discriminatory strength of the classification was confirmed for OMD patients treated with metastases-directed SBRT. Larger multicenter trials are needed to validate the prognostic power for OMD patients irrespective of primary tumor and treatment approach

Dosimetric Analysis of Proximal Bronchial Tree Subsegments to Assess The Risk of Severe Toxicity After Stereotactic Body Radiation Therapy of Ultra-central Lung Tumors

Background and purpose Stereotactic body radiotherapy (SBRT) of ultra-central lung tumors (UCLT) is associated with an increased risk of severe toxicity. The aim of this study was to perform a detailed dosimetric analysis of the proximal bronchial tree (PBT) anatomical sub-segments to evaluate the safety of risk-adapted SBRT and to evaluate potential differences in radiation tolerance between PBT sub-segments. Material and methods Fifty-seven patients treated with SBRT for UCLT between 2014 and 2021 were included. UCLT were defined as tumor abutting or overlapping with the trachea, PBT, or esophagus. This study analyzed overall survival, local control, progression-free survival, and grade ≥3 toxicity events. Bayesian inference was used to build a dose-response model with upper limits for toxicity. Results Twenty-seven (47.4%) of the irradiated lesions were primary or locoregionally recurrent NSCLC and 30 (52.6%) oligometastases. All patients were treated with risk-adapted SBRT of median 45.0 Gy (range: 30.0-60.0 Gy) in 8 or 10 fractions. Grade ≥3 radiation pneumonitis was observed in two patients (3.5%), while no bronchial stenosis, hemorrhage or fistula were observed. The dose-response model predicted a grade ≥3 toxicity (stenosis, hemorrhage or fistula) limited to 4.9% (0 - 11.4%) when delivering EQD2$\_$3 = 100 Gy to any location of the PBT (D0.2cc). Detailed dosimetric analysis of PBT substructures showed no variation in the dose-response model between the anatomical PBT sub-segments. Conclusion Risk-adapted SBRT regimens delivered in 8 or 10 fractions for ultra-central lung tumors resulted in high rates of local tumor control with low toxicity rates, without differences in radiation tolerance between the anatomical PBT sub-segments

Dosimetric analysis of 17 cardiac Sub-structures, Toxicity, and survival in ultra central lung tumor patients treated with SBRT

•Data on cardiac toxicity after SBRT for ultra-central lung tumors remains limited.•We analyzed the dose to 18 cardiac sub-structures and cardiovascular toxicity.•A SBRT regimen of 45 Gy in 8-10 fractions yields good local control and low toxicity.•The highest cardiac doses were observed in the pulmonary artery and left atrium.•Higher doses to the base of the heart seem to be associated with non-cancer deaths