To report outcome (freedom from local progression [FFLP], overall survival [OS] and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO).Adrenal metastases treated with SBRT (≤12 fractions, biologically effective dose [BED10] ≥ 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). Three hundred twenty-six patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall-RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%).Unadjusted FFLP was higher after SBRT vs Pall-RT (P = .026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression.Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. One-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway.

IntroductionThis article seeks to identify where delays occur along the adult HIV care cascade (“the cascade”), to improve understanding of what constitutes “delay” at each stage of the cascade and how this can be measured across a range of settings and to inform service delivery efforts. Current metrics are reviewed, measures informed by global guidelines are suggested and areas for further clarification are underscored.DiscussionQuestions remain on how best to evaluate late entry into each stage of the cascade. The delayed uptake of HIV testing may be more consistently measured once rapid CD4 testing is administered at the time of HIV testing. For late enrolment, preliminary research has begun to determine how different time intervals for linking to HIV care affect individual health. Regarding treatment, since 2013, the World Health Organization (WHO) and UNAIDS recommend treatment initiation when CD4 <500 cells/mm3; these guidelines provide a useful albeit evolving threshold to define late treatment initiation. Finally, WHO guidelines for high-, low- and middle-income countries also could be used to standardize measures for achieving viral suppression.ConclusionsThere is no “one size fits all” model as the provision of services may differ based on a range of factors. Nonetheless, measures informed by global guidelines are needed to more consistently evaluate the scope of and factors associated with delays to each stage of the cascade. Doing so will help identify how practitioners can best deliver services and facilitate access to and continued engagement in care.

Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n ¼ 82) or ipilimumab and additional LPT (n ¼ 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P ¼ 0.0028). Adverse immunerelated events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P ¼ 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation.

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The best predictive accuracy for presence of TBI was obtained using the GCS components. Pupil reactivity together with the GCS motor component performed best in predicting death.

OBJECTIVE Prediction of death and functional outcome is essential for determining treatment strategies and allocation of resources for patients with severe traumatic brain injury (TBI). The aim of this study was to evaluate, by using pupillary status and Glasgow Coma Scale (GCS) score, if patients with severe TBI who are ≤ 15 years old have a lower mortality rate and better outcome than adults with severe TBI. METHODS A retrospective cohort analysis of patients suffering from severe TBI registered in the Trauma Registry of the German Society for Trauma Surgery between 2002 and 2013 was undertaken. Severe TBI was defined as an Abbreviated Injury Scale of the head (AIS) score of ≥ 3 and an AIS score for any other part of the body that does not exceed the AIS score. Only patients with complete data (GCS score, age, and pupil parameters) were included. To assess the impact of GCS score and pupil parameters, the authors also used the recently introduced Eppendorf-Cologne Scale and divided the study population into 2 groups: children (0-15 years old) and adults (16-55 years old). Each patient's outcome was measured at discharge from the trauma center by using the Glasgow Outcome Scale. RESULTS A total of 9959 patients fulfilled the study inclusion criteria; 888 (8.9%) patients were ≤ 15 years old (median 10 years). The overall mortality rate and the mortality rate for patients with a GCS of 3 and bilaterally fixed and dilated pupils (19.9% and 16.3%, respectively) were higher for the adults than for the pediatric patients (85% vs 80.9%, respectively), although cardiopulmonary resuscitation rates were significantly higher in the pediatric patients (5.6% vs 8.8%, respectively). In the multivariate logistic regression analysis, no motor response (OR 3.490, 95% CI 2.240-5.435) and fixed pupils (OR 4.197, 95% CI 3.271-5.386) and bilateral dilated pupils (OR 2.848, 95% CI 2.282-3.556) were associated with a higher mortality rate. Patients ≤ 15 years old had a statistically lower mortality rate (OR 0.536, 95% CI 0.421-0.814; p = 0.001). The rate of good functional outcomes (Glasgow Outcome Scale Score 4 or 5) was higher in pediatric patients than in the adults (72.2% vs 63.1%, respectively). CONCLUSIONS This study found that severe TBI in children aged ≤ 15 years is associated with a lower mortality rate and superior functional outcome than in adults. Also, children admitted with a missing motor response or fixed and bilaterally dilated pupils also have a lower mortality rate and higher functional outcome than adults with the same initial presentation. Therefore, patients suffering from severe TBI, especially pediatric patients, could benefit from early and aggressive treatment.