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

Involved-field radiotherapy for patients with mantle cell lymphoma

Introduction: Retrospective analysis was performed at a single institution to assess the responsiveness of mantle cell lymphoma (MCL) to involved-field radiotherapy (IFRT). Methods: All patients treated with IFRT to at least one site of MCL between 1998 and 2012 were included. There were 25 patients who received radiotherapy to 60 disease sites. Primary endpoint was overall response rate (ORR) infield for the first site of MCL treated per patient. Predictors of ORR were analysed for the primary endpoint. Time to local progression (TLP) infield and progression-free survival were calculated from the start of the first treatment course. Analysis of all sites collectively was also undertaken. Survival analysis was conducted by the Kaplan-Meier method. Results: ORR rate was 84% for the first site treated per patient. Complete response and partial response rates were 68% and 16% respectively. Median TLP following radiotherapy to the first site was not reached. Infield control rate was 91% at 12 months (95% confidence interval 69-97%). When analysis was performed on all 60 sites, ORR was 85%. Symptomatic improvement occurred after IFRT to 93% of all sites. Systemic progression outside the radiotherapy field was the predominant form of failure following IFRT. Conclusion: Radiotherapy generally induced a clinical response at all levels of dose administered, ranging from 3 to 36Gy. However, increased durability of local control was suggested with higher doses. Radiotherapy is an effective treatment for palliation of MCL with objective and symptomatic responses seen over a range of radiotherapy doses

T1-2 anal carcinoma requires elective inguinal radiation treatment: The results of Trans Tasman Radiation Oncology Group study TROG 99.02

Background and purpose: Elective inguinal irradiation increases morbidity. We describe outcomes of moderate intensity chemoradiation treating anal canal and adjacent pelvic nodes only. Material and methods: Forty patients with T1-2, N0 anal carcinoma were enrolled between March 1999 and March 2003. Inguinal nodes were NOT electively irradiated. The anal canal and regional pelvic nodes received 36 Gy/20# over 4 weeks, and 2 weeks later the anal canal was boosted with 14.4 Gy/8#. Chemotherapy was 5 fluorouracil 800 mg/m /day on days 1-4 and 36-39, and Mitomycin C 10 mg/m on day 1. Results: Median follow-up was 44 months. Complete response was 95%. Four year results were; overall survival 71%, local control 82%, and colostomy-free survival (including salvage) 85%. Inguinal failure occurred in 22.5% but was isolated in only 12.5%. Treatment was well tolerated acutely with no toxic deaths. Severe late toxicity occurred in 7.5%. Conclusions: This moderate dose 'non inguinal' chemoradiation regimen resulted in modest acute toxicity, minimal long term morbidity and local control in line with other series. However staging failed to identify 12.5% of patients whose isolated inguinal failure might have been prevented by elective irradiation. Without more effective staging, all patients should receive elective inguinal irradiation

A paired, double-blind, randomized comparison of a moisturizing durable barrier cream to 10% glycerine cream in the prophylactic management of postmastectomy irradiation skin care: Trans Tasman Radiation Oncology Group (TROG) 04.01

Abstract not availablePeter H. Graham, Natalie Plant, Jennifer L. Graham, Lois Browne, Martin Borg, Anne Capp, Geoff P. Delaney, Jennifer Harvey, Lisbeth Kenny, Michael Francis and Yvonne Zissiadi

Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53

The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. The ER+ tumours were classified as ‘luminal A’ (LA): ER+ and/or PR+, Ki-67 low, p53-, HER2- or ‘luminal B’ (LB): ER+ and/or PR+ and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS). In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6-19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555-8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501-6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629-8.031, P=0.002) but not IBTR. The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy

Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel

The aim of this study was to determine the clinical utility of intrinsic molecular phenotype after breast-conserving therapy (BCT) with lumpectomy and whole-breast irradiation with or without a cavity boost. Four hundred ninety-eight patients with invasive breast cancer were enrolled into a randomized trial of BCT with or without a tumor bed radiation boost. Tumors were classified by intrinsic molecular phenotype as luminal A or B, HER-2, basal-like, or unclassified using a five-biomarker panel: estrogen receptor, progesterone receptor, HER-2, CK5/6, and epidermal growth factor receptor. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ipsilateral breast tumor recurrence (IBTR), locoregional recurrence (LRR), distant disease-free survival (DDFS), and death from breast cancer. Median follow-up was 84 months. Three hundred ninety-four patients were classified as luminal A, 23 were luminal B, 52 were basal, 13 were HER-2, and 16 were unclassified. There were 24 IBTR (4.8%), 35 LRR (7%), 47 distant metastases (9.4%), and 37 breast cancer deaths (7.4%). The overall 5-year disease-free rates for the whole cohort were: IBTR 97.4%, LRR 95.6%, DDFS 92.9%, and breast cancer–specific death 96.3%. A significant difference was observed for survival between subtypes for LRR (P = .012), DDFS (P = .0035), and breast cancer–specific death (P = .0482), but not for IBTR (P = .346). The 5-year and 10-year survival rates varied according to molecular subtype. Although this approach provides additional information to predict time to IBTR, LRR, DDFS, and death from breast cancer, its predictive power is less than that of traditional pathologic indices. This information may be useful in discussing outcomes and planning management with patients after BCT

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease