4093 Background: Early-stage hepatocellular carcinoma (HCC) can be treated with liver resection (LR), but up to 70% of patients experience relapse within two years after surgery. Despite their established use in advanced disease, immune checkpoint inhibitors (ICPI) are still under investigation in the peri-operatory setting. Methods: PRIME‐HCC is a phase Ib study investigating safety and bioactivity of the nivolumab (3 mg/kg, day 1 and day 22) plus ipilimumab (1mg/kg, day 1 only) combination (Nivo+Ipi) prior to LR in early-stage HCC. The primary safety analysis assessed treatment-related adverse events (trAE) and delays to surgery. Secondary endpoint included objective response rate (ORR) by RECIST v1.1 and pathologic response rate on resection specimens. Results: At data censoring on the 27th of January 2022, 17 patients were enrolled, of whom 82% (n = 14) were male, with a median age of 64 years (range 47-76). Performance status was 0 in 88% of patients (n = 15) according to the Eastern Cooperative Oncology Group scale. Liver cirrhosis was found in 65% (n = 11) of the patients, mostly secondary to viral hepatitis (41%, n = 7). All patients were Child-Pugh A, with 53% (n = 9) classified as albumin-bilirubin (ALBI) grade 2, and the rest grade 1. Median tumour diameter was 3.4 cm (interquartile range [IQR] 2.4-4.0), and the median number of liver nodules was 1 (range 1-3). Any-grade trAEs were reported by 73% of the patients receiving at least one dose of treatment (n = 11, tot n = 15). Four patients (27%) reported grade 2 trAEs including hypothyroidism (n = 2), diarrhoea (n = 1), and fatigue (n = 1), and one (7%) grade 3 ALT/AST elevation. After a median follow-up of 6.3 months (IQR 1.9-23.0), no deaths had occurred. One patient had experienced relapse 20.8 months after treatment commencement, and he achieved partial response to subsequent treatment with atezolizumab plus bevacizumab. Median time to LR from screening was 2.5 months (IQR 2.3-3.2). Only one patient had a surgery delay due to liver function worsening (ICPI-unrelated) and experienced disease progression 12.4 months post-screening. One patient was found to have cholangiocarcinoma (CCA) on LR specimen and was excluded from efficacy analyses. Of the 13 patients with an available radiological assessment, ORR was 23%, with two partial responses and one complete response. Disease control rate was 92%, with one patient with mixed HCC/CCA histology showing primary progression. Of the nine pathologically evaluable patients, seven (78%) achieved a pathological response, including two (22%) complete responses. Conclusions: Nivo+Ipi can be safely administered in the neoadjuvant setting for HCC and does not delay LR. The combination demonstrates promising evidence of anti-tumour efficacy in terms of radiological and pathological response. Clinical trial information: NCT03682276.
BACKGROUND: Brachial plexus blocks, alone or in combination with general anesthesia, has become one of the most important anesthesia techniques for surgeries in the upper limb. Prolongation of analgesia using perineural catheters are not yet popular, and we are in need for an adjuvant that can prolong the action of local anesthetics after single injection peripheral nerve blocks. Dexamethasone and clonidine are two commonly used adjuvants. This study was undertaken to compare the analgesic efficacy of dexamethasone and clonidine. MATERIALS AND METHODS: Ninety adult patients fitting under the inclusion criteria were assigned to three groups of thirty each and received ultrasound guided supraclavicular brachial plexus block. They received either dexamethasone 8 mg (Group D) or clonidine 1mcg/kg (Group C) or saline 2 ml (Group S) with 15 ml of 0.5% bupivacaine. The onset of sensory and motor blocks, duration of analgesia and the duration of motor block were assessed. RESULTS: The onset of sensory and motor block were comparable in all the three groups (17.50±2.86 minutes and 30.33±4.14 minutes; 17.17±3.13 minutes and 31.0±4.8 minutes; 18.33±3.55 minutes and 31.0±5.48 minutes for groups D, C and S respectively. The duration of analgesia and motor blockade was markedly prolonged in dexamethasone group (19.41±2.60 hours and 17.19±2.13 hours) and moderately prolonged clonidine group (11.49±1.66 hours and 10.41±1.18 hours) when compared to saline group (7.56±1.65 hours and 6.22±1.43 hours). CONCLUSION: Dexamethasone proves to be a better adjuvant compared to clonidine, as it considerably prolongs analgesia and is devoid of significant side effects. But the prolonged motor block is still a matter of concern and the search for an adjuvant that selectively prolongs analgesia without impairing motor function continues.
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