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Objective: Epithelioid sarcoma (ES) presents unique clinical features in comparison to other sarcoma subtypes. Data regarding the benefits of chemotherapy are very limited. Combination regimens using gemcitabine and docetaxel (Gem/Doce) have proven to be effective, especially in uterine and nonuterine leiomyosarcoma. Yet, there is no available data on the efficacy of Gem/Doce in ES. Methods: A retrospective analysis of the three participating institutions was performed. Twenty-eight patients with an ES diagnosis presented at one of the participating institutions between 1989 and 2012. Of this group, 17 patients received chemotherapy. Results: Patients' median overall survival (OS) after the beginning of palliative chemotherapy was 21 months, and the 1-year OS was 87%. Twelve patients received Gem/Doce with a clinical benefit rate of 83%. The median progression-free survival (PFS) was 8 months for all patients receiving Gem/Doce. The best response was complete remission in 1 patient and partial remission in 6 patients. All 6 patients receiving Gem/Doce as a first-line treatment showed measurable responses with a median PFS of 9 months. Conclusions: In this retrospective study, Gem/Doce was an effective chemotherapeutic regimen for ES. Prospective studies are needed to better assess the effects of this combination drug therapy.
Individual responses to behavioral treatment of anxiety disorders vary considerably, which requires a better understanding of underlying processes. In this study, we examined the violation and change of threat beliefs during exposure. From 8,484 standardized exposure records of 605 patients with different anxiety disorders, learning indicators were derived: expectancy violation as mismatch between threat expectancy before exposure and threat occurrence, expectancy change as difference between original and adjusted expectancy after exposure, and prediction-error learning rate as extent to which expectancy violation transferred into change. Throughout sessions, high threat expectancy but low occurrence and adjusted expectancy indicated successful violation and change of threat beliefs by exposure. Expectancy violation, change, and learning rate substantially varied between patients. Not expectancy violation itself, but higher learning rate and expectancy change predicted better treatment outcome. Successful exposure thus requires expectancy violation to induce actual expectancy change, supporting learning from prediction error as transdiagnostic mechanism underlying successful exposure therapy.
Abstract
Background
The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions.
Methods
This multicenter randomized controlled trial compared two variants of prediction error‐based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx‐I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx‐S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6‐months follow‐up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression.
Results
Both treatments resulted in substantial improvements at post (PeEx‐I: dwithin = 1.50, PeEx‐S: dwithin = 1.78) and follow‐up (PeEx‐I: dwithin = 2.34; PeEx‐S: dwithin = 2.03). Both groups showed formally equivalent symptom reduction at post and follow‐up. However, time until response during treatment was 32% shorter in PeEx‐I (median = 68 days) than PeEx‐S (108 days; TRPeEx‐I = 0.68). Interestingly, drop‐out rates were lower during intensified exposure. PeEx‐I was also superior in reducing disability days and improving quality of life at follow‐up without increasing relapse.
Conclusions
Both treatment variants focusing on the transdiagnostic exposure‐based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop‐out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.