OBJECTIVE To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). METHODS Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). RE-SULTS Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3-14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3-24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19-52%, p<0.001) overall, 63% (95%CI=35-79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2-44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19 + B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. CONCLUSION RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.
4505 Background: Patients with borderline resectable pancreatic cancer have poor survival and low resection rates. Neoadjuvant therapy may improve the outcome for these patients. The aim of this trial was to determine the feasibility and efficacy of a comparison of immediate surgery versus neoadjuvant GEMCAP or FOLFIRINOX or CRT. Methods: Eligible patients with NCCN defined borderline resectable (following central review of the baseline CT scan) and biopsy proven pancreatic cancer were randomised (stratified by centre) to receive immediate surgery, or neoadjuvant therapy of either 2 cycles of GEMCAP, or 4 cycles of FOLFIRINOX or 50.4Gy capecitabine-based CRT in 28 daily fractions over 5 ½ weeks. Patients were restaged at 4-6 weeks and underwent surgical exploration if still borderline resectable. Resected patients received adjuvant therapy. Follow up was 12 months. There was quality assurance of surgery and CRT. Primary endpoints were recruitment rate and resection rate (R1/R0). Secondary endpoints included overall survival and toxicity. A target of 90 patients was set to determine feasibility and resection rates. Rates will be presented as point estimates and survival compared across treatment arms using a log-rank test. Analyses will be on an ITT basis. Results: Between August 2014 and December 2018, 90 patients were randomised with 88 included in the full analysis set (32 immediate surgery, 20 GEMCAP, 20 FOLFIRINOX, 16 CRT). Median age was 63 years, 44% were men. WHO performance status was 0 and 1 in 45% and 55% respectively. Median CA19-9 was 603 kU/L at baseline. 44 (79%) patients completed neoadjuvant therapy. Recruitment rate was 21 patients per year. Resection rate was 62% for immediate surgery and 55% for neoadjuvant therapy (p=0.668). R0 resection rate on resected patients was 15% and 23% respectively (p=0.721). One year survival rate was 40% [95% CI, 26% – 62%] for immediate surgery and 77% [95%CI, 66% - 89%] for neoadjuvant therapy. Log-rank analysis showed an HR=0.27 [95% CI, 0.13 – 0.55]; χ2 (1) = 14.91, P<0.001. 9 out of the 51 neoadjuvant patients included in the safety set reported 12 serious adverse events of grade 3 or above. Conclusions: There was no difference in resection rate between arms, however neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Clinical trial information: 89500674 .
The use of metal stents for drainage of pancreatic fluid collections is associated with improved clinical success, fewer adverse events and reduced bleeding compared to plastic stents.
OBJECTIVES
To develop a simplified version of the Eurolung risk model to predict cardiopulmonary morbidity and 30-day mortality after lung resection from the ESTS database.
METHODS
A total of 82 383 lung resections (63 681 lobectomies, 3617 bilobectomies, 7667 pneumonectomies and 7418 segmentectomies) recorded in the ESTS database (January 2007–December 2018) were analysed. Multiple imputations with chained equations were performed on the predictors included in the original Eurolung models. Stepwise selection was then applied for determining the best logistic model. To develop the parsimonious models, different models were tested eliminating variables one by one starting from the less significant. The models’ prediction power was evaluated estimating area under curve (AUC) with the 10-fold cross-validation technique.
RESULTS
Cardiopulmonary morbidity model (Eurolung1): the best parsimonious Eurolung1 model contains 5 variables. The logit of the parsimonious Eurolung1 model was as follows: −2.852 + 0.021 × age + 0.472 × male −0.015 × ppoFEV1 + 0.662×thoracotomy + 0.324 × extended resection. Pooled AUC is 0.710 [95% confidence interval (CI) 0.677–0.743]. Mortality model (Eurolung2): the best parsimonious model contains 6 variables. The logit of the parsimonious Eurolung2 model was as follows: −6.350 + 0.047 × age + 0.889 × male −0.055 × BMI −0.010 × ppoFEV1 + 0.892 × thoracotomy + 0.983 × pneumonectomy. Pooled AUC is 0.737 (95% CI 0.702–0.770). An aggregate parsimonious Eurolung2 was also generated by repeating the logistic regression after categorization of the numeric variables. Patients were grouped into 7 risk classes showing incremental risk of mortality (P < 0.0001).
CONCLUSIONS
We were able to develop simplified and updated versions of the Eurolung risk models retaining the predictive ability of the full original models. They represent a more user-friendly tool designed to inform the multidisciplinary discussion and shared decision-making process of lung resection candidates.
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