No abstract

DISCLAIMER: This article does not represent the official recommendation of the Cleveland Clinic or CaseWestern Reserve University School of Medicine, nor has it yet been peer reviewed. We are releasing it early, pre-peer review, to allow for quick dissemination/vetting by the scientific/clinical community given the necessity for rapid conservation of personal protective equipment (PPE) during this dire global situation. We welcome feedback from the community.Personal protective equipment (PPE), including face shields, surgical masks, and N95 respirators, is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease (COVID-19) increases exponentially in the United States and worldwide, healthcare provider demand for these necessities is currently outpacing supply. As such, strategies to extend the lifespan of the supply of medical equipment as safely as possible are critically important. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. Some hospitals have already begun using UV-C light to decontaminate N95 respirators and other PPE, but many lack the space or equipment to implement existing protocols. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories, and discuss the dose ranges needed for effective decontamination of critical PPE. We further discuss obstacles to this approach including the possibility that the UV radiation levels vary within BSCs. Effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm −2 , which would take a minimum of 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. Elevating the N95 mask by 48 cm (so that it lies 19 cm from the top of the BSC) would enable the delivery of germicidal doses of UV-C in 62 minutes per side. Effective decontamination of face shields likely requires a much lower UV-C dose, and may be achieved by placing the face shields at the bottom of the BSC for 20 minutes per side. Our results are intended to provide support to healthcare organizations looking for alternative methods to extend their reserves of PPE. We recognize that institutions will require robust quality control processes to guarantee the efficacy of any implemented decontamination protocol. We also recognize that in certain situations such institutional resources may not be available; while we subscribe to the general principle that some degree of decontamination is preferable to re-use without decontamination, we would strongly advise that in such cases at least some degree of on-site verification of UV dose delivery be performed.

No abstract

Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm−2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 μWcm−2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.

Background: Stereotactic body radiation therapy (SBRT) is increasingly used for patients with recurrent and or metastatic tumors. Sarcomas are generally considered not sensitive to radiotherapy and SBRT may allow for increased biological effectiveness. We report intermediate outcomes and toxicity for pediatric, adolescent, and young adult patients treated with SBRT to sites of recurrent and or metastatic sarcoma Procedure: We queried an Institutional Review Board-approved registry of patients treated with SBRT for metastases from pediatric sarcomas. Patients age 29 and below were assessed for local control, survival, and toxicity. Results: Thirty-one patients with a total of 88 lesions met eligibility criteria. Median patient age was 17.9 years at treatment. Sixteen patients were treated with SBRT to >1 site of disease. The median dose was 30 Gy in 5 fractions. The median follow-up time was 7.4 months (range: 0.2 to 31.4 mo). Patients were heavily pretreated with systemic therapy. In 57 lesions with >3 months of radiographic follow-up, the 6-month and 12-month local control rates were 88.3%±4.5% and 83.4%±5.5%, respectively. Radiographic local failures were rare (6/57 in-field, 4/57 marginal). Only 1/88 treated lesions was associated with a radiation-related high-grade toxicity; late grade 3 intestinal obstruction in a re-irradiated field while on concurrent therapy (gemcitabine and docetaxel). No acute grade ≥3 toxicity was observed. Conclusions: SBRT was well tolerated in the majority of patients with favorable local control outcomes. Additional studies will be required to determine the optimal SBRT dose and fractionation, treatment volume, and appropriate concurrent therapies.

No abstract

No abstract

Cancer sequencing efforts have demonstrated that cancer is the most complex and heterogeneous disease that affects humans. However, radiation therapy, one of the most common cancer treatments, is prescribed based on an empiric one-size-fits all approach. We propose that the field of radiation oncology is operating under an outdated null hypothesis: that all patients are biologically similar and should uniformly respond to the same dose of radiation. We have previously developed the Genomic Adjusted Radiation Dose (GARD), a method which accounts for biological heterogeneity and can be utilized to predict optimal RT dose for an individual patient. In this article, we utilize GARD to characterize the biological imprecision of one-size-fits-all RT dosing schemes which result in both over- and under-dosing for the majority of patients treated with RT.To elucidate this inefficiency, and therefore the opportunity for improvement using a personalized dosing scheme, we develop a patient-specific competing hazards-style mathematical model combining the canonical equations for tumor control (TCP) and normal tissue complication probabilities (NTCP). This model simultaneously optimizes tumor control and toxicity by personalizing RT dose using patient-specific genomics. Using data from two prospectively collected cohorts of patients with non-small-cell lung cancer, we validate the competing hazards model by demonstrating that it predicts the results of RTOG 0617. We show how 0617 failure can be explained by the biological imprecision of empiric uniform dose escalation which results in 80% of patients being over-exposed to normal tissue toxicity without potential tumor control benefit. In conclusion, our data reveals a tapestry of radiosensitivity heterogeneity, provides a biological framework that explains the failure of empiric RT dose escalation, and quantifies the opportunity to improve clinical outcomes in lung cancer by incorporating genomics into RT.