Supplementary MaterialsAdditional document 1: Table S1. Deficit Accumulation Frailty Index (DAFI)). A safety assessment will be performed after a 3?cycle run-in phase of nivolumab (240?mg Q2W) to justify escalation for eligible patients to combined nivolumab (240?mg Q2W) and ipilimumab (1?mg/kg Q6W), while the other patients will remain on nivolumab only. RAMONA also includes translational research sub-studies to identify predictive biomarkers, including PD-1 and PD-L1 evaluation at different time points, establishment of organoid cultures and microbiome analyses for response prediction. Discussion The RAMONA trial aims to implement checkpoint inhibitors for elderly patients with advanced ESCC as second line therapy. Novel biomarkers for checkpoint-inhibitor response are analyzed in extensive translational sub-studies. Trial registration EudraCT Number: 2017C002056-86; “type”:”clinical-trial”,”attrs”:”text”:”NCT03416244″,”term_id”:”NCT03416244″NCT03416244, registered: 31.1.2018. Electronic supplementary material The online version of this article (10.1186/s12885-019-5446-2) contains supplementary material, which is available to authorized users. strong class=”kwd-title” Keywords: Esophageal squamous cell cancer, Elderly, Comprehensive geriatric assessment, Checkpoint inhibitors, Personalized medicine, Geriatric oncology Background ESCC may be the 6th Elastase Inhibitor, SPCK leading reason behind cancer-related death world-wide [1]. The condition is certainly diagnosed in advanced tumor levels and in older sufferers [1 often, 2]. Efficiency of chemotherapy in advanced ESCC is poorly defined even now. While most sufferers go through chemotherapy and/or chemo-radiation in initial line based on the Combination process using Paclitaxel and Carboplatin, efficiency Flrt2 of second-line chemotherapy is certainly discouraging [3, 4]. Nevertheless, extremely Kojima et al recently. reported that pembrolizumab considerably improved OS in comparison to chemotherapy (paclitaxel, docetaxel or irinotecan) in sufferers with advanced esophageal or esophagogastric junction carcinoma whose tumors express PD-L1 (Mixed Positive Rating [CPS] 10, irrespective of histology) (median 9.3 vs 6.7 mo; HR 0.69; 95% CI 0.52C0.93; em P /em ?=?0.0074). Operating-system at 12?a few months was 43% vs 20%, respectively. (KEYNOTE 181) [5]. Immunotherapy with antibodies against immune system checkpoints like PD-1/PD-L1 represents a fresh treatment chance with relatively small unwanted effects and initial promising leads to the treating squamous cell carcinoma sufferers [6C8]. Regarding esophageal cancer, primary outcomes from an Asian research indicate efficiency of nivolumab [9]. From 64 pre-treated sufferers seriously, 11 (17, 95% CI 10C28) got a target response and 16 (25, 95% CI 16C37) confirmed steady disease. The median overall survival was 10.8?months (IQR 4.9C14.3) in Elastase Inhibitor, SPCK this trial populace (unselected for PD-L1 expression status). Long-term survival was also improved by pembrolizumab as described by Doi et al. [10]. Furthermore, the CheckMate 012 trial exhibited that overall response rates could be doubled when PD-1 inhibitor nivolumab was combined with CTLA-4-inhibitor ipilimumab in advanced NSCLC patients [11]. In this trial, grade 3 and 4 Elastase Inhibitor, SPCK adverse events were reported to occur in 33% of the patients treated with the combination therapy (nivolumab 3?mg/kg Q2W and ipilimumab 1?mg/kg Q6W). In the checkmate 032 in turn (nivolumab 3?mg/kg Q2W and ipilimumab 1?mg/kg Q3W), treatment related adverse events of grade 3 and 4 were only slightly enhanced when compared to nivolumab monotherapy (13% vs. 19%) [12]. There is an increasing need for improved treatment strategies for elderly ESCC patients. These strategies have to acknowledge the challenges of functional limitations and comorbidities in this increasing populace. Elastase Inhibitor, SPCK With increasing age, elderly patients develop chronic diseases and different comorbidities that may affect persons capabilities, functional reserve and life expectancy [13]. However, assessment of these characteristics in the elderly populace is time-consuming, therefore new assessment and screening tools are being developed. The poor knowledge of the role of chemotherapy and immunotherapy in.