Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial
BMC CANCER
Authors: Lieverse, Relinde I. Y.; Van Limbergen, Evert J.; Oberije, Cary J. G.; Troost, Esther G. C.; Hadrup, Sine R.; Dingemans, Anne-Marie C.; Hendriks, Lizza E. L.; Eckert, Franziska; Hiley, Crispin; Dooms, Christophe; Lievens, Yolande; de Jong, Monique C.; Bussink, Johan; Geets, Xavier; Valentini, Vincenzo; Elia, Giuliano; Neri, Dario; Billiet, Charlotte; Abdollahi, Amir; Pasquier, David; Boisselier, Pierre; Yaromina, Ala; De Ruysscher, Dirk; Dubois, Ludwig J.; Lambin, Philippe
Abstract
BackgroundAbout 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit and new treatment strategies are therefore needed. We previously demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-ED-B scFv L19 antibody coupled to IL2, combined with stereotactic ablative radiotherapy (SABR).MethodsThis investigator-initiated, multicentric, randomised controlled open-label phase II clinical trial will test the hypothesis that the combination of SABR and L19-IL2 increases progression free survival (PFS) in patients with limited metastatic NSCLC. One hundred twenty-six patients will be stratified according to their metastatic load (oligo-metastatic: <= 5 or poly-metastatic: 6 to 10) and randomised to the experimental-arm (E-arm) or the control-arm (C-arm). The C-arm will receive SOC, according to the local protocol. E-arm oligo-metastatic patients will receive SABR to all lesions followed by L19-IL2 therapy; radiotherapy for poly-metastatic patients consists of irradiation of one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC). The accrual period will be 2.5-years, starting after the first centre is initiated and active. Primary endpoint is PFS at 1.5-years based on blinded radiological review, and secondary endpoints are overall survival, toxicity, quality of life and abscopal response. Associative biomarker studies, immune monitoring, CT-based radiomics, stool collection, iRECIST and tumour growth rate will be performed.DiscussionThe combination of SABR with or without ICI and the immunocytokine L19-IL2 will be tested as 1st, 2nd or 3rd line treatment in stage IV NSCLC patients in 14 centres located in 6 countries. This bimodal and trimodal treatment approach is based on the direct cytotoxic effect of radiotherapy, the tumour selective immunocytokine L19-IL2, the abscopal effect observed distant from the irradiated metastatic site(s) and the memory effect. The first results are expected end 2023.Trial registrationImmunoSABR Protocol Code: NL67629.068.18; EudraCT: 2018-002583-11; Clinicaltrials.gov: NCT03705403; ISRCTN ID: ISRCTN49817477; Date of registration: 03-April-2019.
Non-significant association between-330 T/G polymorphism in interleukin-2 gene and chronic periodontitis: findings from a meta-analysis
BMC ORAL HEALTH
Authors: da Silva, Felipe Rodolfo Pereira; Galeno, Juliana Gomes; Leal, Alessandro Luiz Araujo Bentes; Koga, Reyce Santos; Batista, Nayana Yared; da Conceicao Furtado, Silvania; Vasconcelos, Daniel Fernando Pereira; Carvalho, Marcelo Diniz; Barcellos, Jose Fernando Marques
Abstract
Background Chronic periodontitis (CP) is an immune-inflammatory disease that promotes tissue damage around the teeth. Among the several inflammatory mediators that orchestrate the periodontitis, there is the interleukin (IL)-2. Genetic variations in IL2 gene may be associated with the risk and severity of the disease. Contrary results are available in the literature with inconclusive findings and none meta-analysis to gather these data. Methods A literature search was performed for studies published before June 11, 2019 in diverse scientific and educational databases. The data was extracted by two investigators and the statistical evaluation was performed by Review Manager statistical program with heterogeneity (I-2) and Odds Ratio (OR) with 95% of Confidence Intervals (CI) calculations and a sensitive analysis to assess the accuracy of the obtained results. The publication bias was evaluated by Begg' and Egger's test with Comprehensive meta-analysis software. The value of P < 0.05 was considered as significant. Results Five studies were identified in diverse ethnical groups with 1425 participants. The - 330 T/G polymorphism in IL2 gene was not significantly associated with CP in allelic evaluation (P > 0.05) as well as in the genotypic comparisons (P = 0.15). The Begg's test and the linear regression Egger's test did not show any evidence of publication bias risk (P > 0.05) which was corroborated by the absence of obvious asymmetry in Funnel plot graphic. Conclusions This meta-analysis showed a non-significant association between - 330 T/G polymorphism in IL2 gene and CP in any allelic evaluation.