Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Initial Experience Treating Lung Tumors with the CyberKnife

Stereotactic body radiosurgery (SBRS) of lung tumors with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) achieves excellent rates of local disease control with limited toxicity to surrounding tissues. We retrospectively reviewed treatments and outcomes for 90 patients with 109 lung lesions treated at the CyberKnife Center of Miami between March 2004 and September 2006. This monotherapy review included 49 patients with 53 primary lung cancers, 27 patients with 42 pulmonary metastases, 6 patients with external beam failure and 8 patients treated by SBRS as a boost following or before conventionally fractionated radiotherapy (3DCRT or IMRT). In the primary tumor category, 43 patients remain alive. Thirty-two have been followed 1 to 25 months (median = 11.5 months). Fortynine percent (21/43) of them have had a complete radiographic response and have been followed for a median of 18.5 months. Another 8 have evidence of at least a partial radiographic response. There have been 5 failures (5/43) within the PTV, for a local recurrence rate of 11%. Of the total 109 treated lesions, 97/109 (89%) showed radiographic evidence of at least a partial response to treatment. Six of the failures were in lesions 100 cc. All of the patients tolerated SBRS well with fatigue as the main toxicity. Two patients required hospitalization for Grade III radiation pneumonitis. We conclude that the delivery of precisely targeted, high dose, hypofractionated irradiation to lung tumors with the CyberKnife is well tolerated and has outcomes that are comparable with published results for other methods of SBRS