IntroductionDrug-based treatment regimens for cancer are often associated with off-target toxic side effects and low penetration of the drug at the tumor site leading to patient morbidity and limited efficacy. Locoregional drug delivery has the potential to increase efficacy while concomitantly reducing toxicity. Areas coveredClinical applications using loco-regional delivery include intra-arterial drug delivery in retinoblastoma, direct intra-tumoral (IT) injection of ethanol for ablation in hepatocellular carcinoma (HCC) and the use of HIPEC in peritoneal carcinomas. In recent years, there has been a significant increase in both approved products and clinical trials, with a particular emphasis on drug delivery platforms such as drug eluting beads for HCC and hydrogel platforms for intravesical delivery in bladder cancer. Expert opinionDevelopment of loco-regional drug delivery systems has been slow, limited by weak clinical data for early applications and challenges relating to dosing, delivery and retention of drugs at the site of action. However, there is increasing focus on the potential of loco-regional drug delivery when combined with bespoke drug delivery platforms. With the growth in immunotherapies, the use of IT delivery to drive priming of the anti-tumor response has opened up a new field of opportunity for locoregional drug delivery.

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Background Minimally invasive intratumoural administration of thermoresponsive hydrogels, that transition from liquid to gel in response to temperature, has been proposed as a potential treatment modality for solid tumours. The aim of this study was to assess the inherent cytotoxicity of a poloxamer-based thermoresponsive hydrogel in a murine xenograft model of lung cancer. Methods In vitro viability assessment was carried out in a lung cancer (A549) and non-cancerous (Balb/c 3T3 clone A31) cell line. Following intratumoural administration of saline or the thermoresponsive hydrogel to an A549 xenograft model in female Athymic Nude-Foxn1nu mice (n = 6/group), localisation was confirmed using IVIS imaging. Tumour volume was assessed using callipers measurements over 14 days. Blood serum was analysed for liver and kidney damage and ex vivo tissue samples were histologically assessed. Results The thermoresponsive hydrogel demonstrated a dose-dependent cancer cell-specific toxicity in vitro and was retained in situ for at least 14 days in the xenograft model. Tumour volume increase was statistically significantly lower than saline treated control at day 14 (n = 6, p = 0.0001), with no associated damage of hepatic or renal tissue observed. Conclusions Presented is a poloxamer-based thermoresponsive hydrogel, suitable for intratumoural administration and retention, which has demonstrated preliminary evidence of local tumour control, with minimal off-site toxicity.

immunotherapies is a key challenge in oncology. Notably, tumor mutational burden detected by tissue next generation sequencing (NGS) was found to be correlated with response to immune checkpoint inhibitors. Methods: In this retrospective study, data were collected on NSCLC patients treated in multiple medical centers in Israel between 2014 and 2017. We used NGS on cell-free circulating tumor DNA (ctDNA) to evaluate whether mutational burden influences the response to immunotherapy in these patients. Results: Overall, 336 NSCLC patients underwent NGS on ctDNA. Of these 336 patients, 192 (57%) were females and 144 (43%) were males. The average age (range) was 64 (23-103) years. Clinical treatment information is currently available for 117 patients, of whom 50 (43%) received immune check-point inhibitors. Rates of stable disease, partial and complete responses (RECIST criteria), as well as progression-free survival and overall survival will be reported. In addition, to unravel the genomic determinants of response to immunotherapy we will use the blood-derived ctDNA to understand if hypermutated ctDNA is a predictive biomarker of response to immunotherapy. Conclusions: ctDNA collection was feasible in 336 patients. Prediction model to associate the ctDNA signature with response to immunotherapy will be presented.