Resection with intraoperative cesium-131 brachytherapy as salvage therapy for recurrent brain tumors.

OBJECTIVE: The authors' objective was to examine the safety and efficacy of salvage intracranial cesium-131 brachytherapy in combination with resection of recurrent brain tumors. METHODS: The authors conducted a retrospective chart review of consecutive patients treated with intraoperative intracranial cesium-131 brachytherapy at a single institution. Permanent suture-stranded cesium-131 seeds were implanted in the resection cavity after maximal safe tumor resection. The primary outcomes of interest were local, locoregional (within 1 cm), and intracranial control, as well as rates of overall survival (OS), neurological death, symptomatic adverse radiation effects (AREs), and surgical complication rate graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Between 2016 and 2020, 36 patients received 40 consecutive cesium-131 implants for 42 recurrent brain tumors and received imaging follow-up for a median (interquartile range [IQR]) of 17.0 (12.7-25.9) months. Twenty patients (55.6%) with 22 implants were treated for recurrent brain metastasis, 12 patients (33.3%) with 16 implants were treated for recurrent atypical (n = 7) or anaplastic (n = 5) meningioma, and 4 patients (11.1%) were treated for other recurrent primary brain neoplasms. All except 1 tumor (97.6%) had received prior radiotherapy, including 20 (47.6%) that underwent 2 or more prior radiotherapy treatments and 23 (54.8%) that underwent prior resection. The median (IQR) tumor size was 3.0 (2.3-3.7) cm, and 17 lesions (40.5%) had radiographic evidence of ARE prior to salvage therapy. Actuarial 1-year local/locoregional/intracranial control rates for the whole cohort and patients with metastases and meningiomas were 91.6%/83.4%/47.9%, 88.8%/84.4%/45.4%, and 100%/83.9%/46.4%, respectively. No cases of local recurrence of any histology (0 of 27) occurred after gross-total resection (p = 0.012, log-rank test). The 1-year OS rates for the whole cohort and patients with metastases and meningiomas were 82.7%, 79.1%, and 91.7%, respectively, and the median (IQR) survival of all patients was 26.7 (15.6-36.4) months. Seven patients (19.4%) experienced neurological death from progressive intracranial disease (7 of 14 total deaths [50%]), 5 (13.9%) of whom died of leptomeningeal disease. Symptomatic AREs were observed in 9.5% of resection cavities (n = 4), of which 1 (2.4%) was grade 3 in severity. The surgical complication rate was 16.7% (n = 7); 4 (9.5%) of these patients had grade 3 or higher complications, including 1 patient (2.4%) who died perioperatively. CONCLUSIONS: Cesium-131 brachytherapy resulted in good local control and acceptable rates of symptomatic AREs and surgical complications in this heavily pretreated cohort, and it may be a reasonable salvage adjuvant treatment for this patient population.

Effect of massage on percutaneous penetration and skin decontamination: man and animal.

CONTEXT: At least 15 factors of percutaneous penetration exist that should be considered when investigating dermal absorption profiles of chemicals. Rubbing is one variable that has been understudied, but may play an important role in understanding overall exposure rates, chemical toxicity, dermal absorption and skin's barrier abilities. OBJECTIVE: This reviews current data related to the role of massage in enhancing percutaneous penetration and skin decontamination as well as highlights the need for further investigation of its role. RESULTS: An in vivo study in rhesus monkeys and guinea pigs measuring amount of drug excreted after being topically applied showed no effect with massage. However, studies measuring permeation rates directly through human and animal skin ex vivo showed rubbing increased flux, reduced skin impedance and increased drug retention in skin. Rubbing also increased effectiveness of reactive skin decontamination lotion (RSDL). CONCLUSION: Massage sometimes influences chemical penetration rates and should be studied thoroughly to clarify the mechanisms and factors involved in the possible enhancing effect. This will also reveal more insight regarding the skin's ability to act as a barrier to exogenous substances and its role in risk assessment. How ex vivo results translate to in vivo behaviors still requires further investigation.

Discontinued dermatological drugs in 2014.

INTRODUCTION: Dermatology is a relatively small field concerned with conditions of the hair, skin, nails and their related diseases; yet there is considerable active research and development within the field. Pharmaceutical companies seek more effective treatments through various therapeutic classes and delivery routes. However, 28 drugs have been discontinued for the treatment of dermatologic diseases in 2014. AREAS COVERED: Herein, the authors summarize the details about each discontinued drug in 2014. The dermatological conditions covered are: psoriasis, eczema, leg ulcers, wounds, allergies, acne, scleroderma, lupus erythematosus, urticaria, mastocytosis, epidermolysis bullosa, onychomycosis and one other unspecified disease. The authors also provide suggestions for improving and accelerating the future of dermatological drug development. EXPERT OPINION: It is clear that improved metrics, especially for early assessment, emphasizing clinical relevance, are necessary to increase success rate. Transparency and clear communication within the field is necessary to reduce and salvage the waste that accumulates from these costly studies. Focused attention on how preclinical and early clinical studies failed to indicate subsequent toxicity profiles in patients would accelerate drug development. Distinguishing between disappointing study results and business/financial factors is important when analyzing discontinuations. A reformed approach toward study design would aid both. Ultimately, relevance and practicality for the patient must be kept in mind at all times.