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Multicentre study revealed significant gaps between evidence-based recommendations for using corticosteroids for croup and clinical practice

Aim: Adherence to croup management recommendations has been poorly investigated. This study aimed to describe the treatment patterns in two paediatric emergency departments and analyse the adherence to recommendations. Methods: We conducted a retrospective chart review of children diagnosed with croup in two Italian paediatric emergency departments in 2017. Data on clinical presentation, corticosteroid administration and home therapy were collected. Length of stay, hospitalisation and re-access rates were compared among different corticosteroid treatment groups. Results: We enrolled 632 patients (61.1% males) with a mean age of 42.8 ± 55.1 months. Corticosteroids were administered to 403 (63.8%) children in the emergency departments. Dexamethasone was administered to 1 (0.4%) patient. Inhaled and oral corticosteroids were given to 342 (54.1%) and 226 (35.8%) patients, respectively. Home therapy was prescribed for 603 (95.4%) patients, either with inhaled (86.2%) and/or oral (43.8%) corticosteroids. The re-access rate was 2.8%. The actual pharmaceutical costs were an estimated 10 times higher than they would have been if the recommendations had been followed. Conclusion: A significant gap between the evidence and clinical practice for croup treatment was observed. Improving adherence to the recommendations could lead to clinical and economic benefits

Liver SBRT with active motion-compensation results in excellent local control for liver oligometastases: An outcome analysis of a pooled multi-platform patient cohort

Background: Local treatment of metastases in combination with systemic therapy can prolong survival of oligo-metastasized patients. To fully exploit this potential, safe and effective treatments are needed to ensure long-term metastases control. Stereotactic body radiotherapy (SBRT) is one means, however, for moving liver tumors correct delivery of high doses is challenging. After validating equal in-vivo treatment accuracy, we analyzed a pooled multi-platform liver-SBRT-database for clinical outcome. Methods: Local control (LC), progression-free interval (PFI), overall survival (OS), predictive factors and toxicity was evaluated in 135 patients with 227 metastases treated by gantry-based SBRT (deep-inspiratory breath-hold-gating; n = 71) and robotic-based SBRT (fiducial-tracking, n = 156) with mean gross tumor volume biological effective dose (GTV-BEDα/β=10Gy) of 146.6 Gy10. Results: One-, and five-year LC was 90% and 68.7%, respectively. On multivariate analysis, LC was significantly predicted by colorectal histology (p = 0.006). Median OS was 20 months with one- and two-year OS of 67% and 37%. On multivariate analysis, ECOG-status (p = 0.003), simultaneous chemotherapy (p = 0.003), time from metastasis detection to SBRT-treatment (≥2months; p = 0.021) and LC of the treated metastases (≥12 months, p < 0.009) were significant predictors for OS. One- and two-year PFI were 30.5% and 14%. Acute toxicity was mild and rare (14.4% grade I, 2.3% grade II, 0.6% grade III). Chronic °III/IV toxicities occurred in 1.1%. Conclusions: Patient selection, time to treatment and sufficient doses are essential to achieve optimal outcome for SBRT with active motion compensation. Local control appears favorable compared to historical control. Long-term LC of the treated lesions was associated with longer overall survival

Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis

The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aims of this study were to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed using Kaplan-Meier and log rank testing. Toxicity was defined by the CTCAE v4.03 criteria. The median FU was 19.9 mo (range 1-102 mo); 1y OS, PFS and LC were 59%, 24% and 84%, respectively. Median TTS was 25.5 mo (95% CI 11-40). TT was started before SRT in 77% of patients. TT was interrupted during SRT in 44% of patients, with a median interruption of 7 (range 1-42) days. There was no significant difference in OS or PFS whether TT was temporarily interrupted during SRT or not. Any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, respectively. The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any-grade toxicity was significantly increased when EGFRi (p = 0.016) or BRAF/MEKi (p = 0.009) were continued during SRT. Severe (≥grade 3) acute and late SRT-related toxicity were observed in 5 (3%) and 7 (4%) patients, respectively, most frequently in patients treated with EGFRi or BRAF/MEKi and in the intracranial cohort. There was no significant difference in severe toxicity whether TT was interrupted before and after SRT or not. In conclusion, SRT and continuous vs. interrupted TT in metastatic cancer patients did not influence OS or PFS. Overall, severe toxicity of combined treatment was rare; a potentially increased toxicity after SRT and continuous treatment with EGFR inhibitors or BRAF(±MEK) inhibitors requires further evaluation

Continued versus interrupted targeted therapy during metastasis-directed stereotactic radiotherapy: a retrospective multi-center safety and efficacy analysis

SIMPLE SUMMARY: The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aim of this study was to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed. We found that there was no significant difference in survival, progression, or severe toxicity, whether TT was interrupted during SRT or not. Although any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, severe SRT-related toxicity rates were low (3% and 4%, respectively). The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any grade of toxicity was significantly increased when EGFRi or BRAF/MEKi were continued during SRT. However, this did not account for severe toxicity. ABSTRACT: The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aims of this study were to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed using Kaplan–Meier and log rank testing. Toxicity was defined by the CTCAE v4.03 criteria. The median FU was 19.9 mo (range 1–102 mo); 1y OS, PFS and LC were 59%, 24% and 84%, respectively. Median TTS was 25.5 mo (95% CI 11–40). TT was started before SRT in 77% of patients. TT was interrupted during SRT in 44% of patients, with a median interruption of 7 (range 1–42) days. There was no significant difference in OS or PFS whether TT was temporarily interrupted during SRT or not. Any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, respectively. The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any-grade toxicity was significantly increased when EGFRi (p = 0.016) or BRAF/MEKi (p = 0.009) were continued during SRT. Severe (≥grade 3) acute and late SRT-related toxicity were observed in 5 (3%) and 7 (4%) patients, respectively, most frequently in patients treated with EGFRi or BRAF/MEKi and in the intracranial cohort. There was no significant difference in severe toxicity whether TT was interrupted before and after SRT or not. In conclusion, SRT and continuous vs. interrupted TT in metastatic cancer patients did not influence OS or PFS. Overall, severe toxicity of combined treatment was rare; a potentially increased toxicity after SRT and continuous treatment with EGFR inhibitors or BRAF(±MEK) inhibitors requires further evaluation

Colonization with multi-drug-resistant organisms negatively impacts survival in patients with non-small cell lung cancer.

ObjectivesMultidrug-resistant organisms (MDRO) are considered an emerging threat worldwide. Data covering the clinical impact of MDRO colonization in patients with solid malignancies, however, is widely missing. We sought to determine the impact of MDRO colonization in patients who have been diagnosed with Non-small cell lung cancer (NSCLC) who are at known high-risk for invasive infections.Materials and methodsPatients who were screened for MDRO colonization within a 90-day period after NSCLC diagnosis of all stages were included in this single-center retrospective study.ResultsTwo hundred and ninety-five patients were included of whom 24 patients (8.1%) were screened positive for MDRO colonization (MDROpos) at first diagnosis. Enterobacterales were by far the most frequent MDRO detected with a proportion of 79.2% (19/24). MDRO colonization was present across all disease stages and more present in patients with concomitant diabetes mellitus. Median overall survival was significantly inferior in the MDROpos study group with a median OS of 7.8 months (95% CI, 0.0-19.9 months) compared to a median OS of 23.9 months (95% CI, 17.6-30.1 months) in the MDROneg group in univariate (p = 0.036) and multivariate analysis (P = 0.02). Exploratory analyses suggest a higher rate of non-cancer-related-mortality in MDROpos patients compared to MDROneg patients (p = 0.002) with an increased rate of fatal infections in MDROpos patients (p = 0.0002).ConclusionsMDRO colonization is an independent risk factor for inferior OS in patients diagnosed with NSCLC due to a higher rate of fatal infections. Empirical antibiotic treatment approaches should cover formerly detected MDR commensals in cases of (suspected) invasive infections

Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy Melanoma brain metastases prognostic score.

Background Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT). Methods This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (<= 30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS. Results One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0-40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03). Conclusion The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively