Phase II trial of domatinostat (4SC-202) in combination with avelumab in patients with previously treated advanced mismatch repair proficient oesophagogastric and colorectal adenocarcinoma: EMERGE.

BACKGROUND: Most oesophagogastric adenocarcinomas (OGAs) and colorectal cancers (CRCs) are mismatch repair proficient (MMRp), responding poorly to immune checkpoint inhibition. We evaluated the safety and efficacy of domatinostat (histone deacetylase inhibitor) plus avelumab (anti-PD-L1 antibody) in patients with previously treated inoperable, advanced/metastatic MMRp OGA and CRC. PATIENTS AND METHODS: Eligible patients were evaluated in a multicentre, open-label dose escalation/dose expansion phase II trial. In the escalation phase, patients received escalating doses of domatinostat [100 mg once daily (OD), 200 mg OD, 200 mg twice daily (BD)] orally for 14 days followed by continuous dosing plus avelumab 10 mg/kg administered intravenously 2-weekly (2qw) to determine the recommended phase II dose (RP2D). The trial expansion phase evaluated the best objective response rate (ORR) during 6 months by RECIST version 1.1 using a Simon two-stage optimal design with 2/9 and 1/10 responses required to proceed to stage 2 in the OGA and CRC cohorts, respectively. RESULTS: Patients (n = 40) were registered between February 2019 and October 2021. Patients in the dose escalation phase (n = 12) were evaluated to confirm the RP2D of domatinostat 200 mg BD plus avelumab 10 mg/kg. No dose-limiting toxicities were observed. Twenty-one patients were treated at the RP2D, 19 (9 OGA and 10 CRC) were assessable for the best ORR; 2 patients with CRC did not receive combination treatment and were not assessable for the primary endpoint analysis. Six patients were evaluated in the dose escalation and expansion phases. In the OGA cohort, the best ORR was 22.2% (95% one-sided confidence interval lower bound 4.1) and the median duration of disease control was 11.3 months (range 9.9-12.7 months). No responses were observed in the CRC cohort. No treatment-related grade 3-4 adverse events were reported at the RP2D. CONCLUSIONS: Responses in the OGA cohort met the criteria to expand to stage 2 of recruitment with an acceptable safety profile. There was insufficient signal in the CRC cohort to progress to stage 2. TRIAL REGISTRATION: NCT03812796 (registered 23rd January 2019).

A survey of liver ablation amongst UK interventional radiologists.

AIM: To characterise training for, and conduct of, image-guided liver tumour ablation amongst UK interventional radiologists. MATERIALS AND METHODS: A web-based survey of British Society of Interventional Radiology members was carried out between 31 August to 1 October 2022. Twenty-eight questions were designed, covering four domains: (1) respondent background, (2) training, (3) current practice, and (4) operator technique. RESULTS: One hundred and six responses were received, with an 87% completion rate and an approximate response rate of 13% of society members. All UK regions were represented, with the majority from London (22/105, 21%). Seventy-two out of 98 (73%) were either extremely or very interested in learning about liver ablation during training, although levels of exposure varied widely, and 37/103 (36%) had no exposure. Performed numbers of cases also varied widely, between 1-10 cases and >100 cases per operator annually. All (53/53) used microwave energy, and most routinely used general anaesthesia (47/53, 89%). Most 33/53 (62%) did not have stereotactic navigation system, and 25/51(49%) always, 18/51 (35%) never, and 8/51(16%) sometimes gave contrast medium (mean 40, SD 32%) after procedures. Fusion software to judge ablation completeness was never used by 86% (43/55), sometimes used by 9% (5/55), and always used by 13% (7/55) of respondents. CONCLUSION: Although there are high levels of interest in image-guided liver ablation amongst UK interventional radiologists, training arrangements, operator experience, and procedural technique vary widely. As image-guided liver ablation evolves, there is a growing need to standardise training and techniques, and develop the evidence base to ensure high-quality oncological outcomes.

Percutaneous cryoablation for desmoid fibromatosis: initial experience at a UK centre.

AIM: To report the first UK experience of cryoablation in desmoid fibromatosis (DF) with particular focus on technique, safety, and efficacy. MATERIALS AND METHODS: Patients were selected at multidisciplinary tumour board meetings at a specialist cancer hospital. Radiation dose, procedure duration, and number of cryoprobes were compared for small versus large tumours (>10 cm long axis). Response at magnetic resonance imaging (MRI) was evaluated using different criteria, and percentage agreement with clinical response as assessed in oncology clinic calculated. RESULTS: Thirteen procedures were performed in 10 patients (eight women, median age 51 years, IQR 42-69 years) between February 2019 and August 2021. Procedures for large tumours had higher radiation dose (2,012 ± 1,012 versus 1,076 ± 519 mGy·cm, p=0.048) used more cryoprobes (13 ± 7 versus 4 ± 2, p=0.009), and were more likely to have residual unablated tumour (38 ± 37% versus 7.5 ± 10%, p=0.045). Adverse events were minor apart from one transient radial nerve palsy. Eight of 10 patients had symptomatic benefit at clinical follow-up (median 353 days, IQR 86-796 days), and three started systemic therapy mean 393 days later. All patients who had complete ablation demonstrated symptomatic response, with no instances of repeat treatment, recurrence, or need for systemic therapy during the study period. All progression occurred outside ablation zones. CONCLUSION: Cryoablation for symptomatic DF is a reproducible technique with low, transient toxicity, where one or two treatments can achieve a meaningful response. Where possible, the ablation ice ball should fully cover DF tumours.

TuLIP (Tunnelled Line Intraluminal Plasty): An Alternative Technique for Salvaging Haemodialysis Catheter Patency in Fibrin Sheath Formation.

BACKGROUND: Renal patients with a tunnelled haemodialysis line are at risk of fibrin 'sheath' formation which can lead to occlusion. Dysfunctional lines are best treated by catheter exchange with a new subcutaneous tunnel; however, there is a risk of scarring, venous stenosis, potential loss of valuable access as well as the risk of infection. METHOD: We report a retrospective review of our experience using tunnelled line intraluminal plasty (TuLIP) in 11 patients over 16 months with fibrin sheath formation on pre-existing tunnelled haemodialysis catheters. RESULT: All patients responded well to treatment with median line patency post TuLIP reaching 112 days. CONCLUSION: TuLIP may have a role in extending catheter lifespan and delaying more invasive intervention.

Excimer laser treatment of spherical hyperopia: PRK or LASIK?

PURPOSE: To compare the efficacy and safety of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in the treatment of spherical hyperopia with use of the VISX STAR S2 excimer laser. METHODS: A review of 15 consecutive patients (22 eyes) receiving PRK and 22 consecutive patients (26 eyes) receiving LASIK (median follow-up, 12 months). RESULTS: Mean age was 52 +/- 7 years for patients receiving PRK and 55 +/- 9 years for patients receiving LASIK. Mean preoperative spherical equivalent was +2.25 +/- 1.16 D for PRK patients and +1.81 +/- 0.92 D for LASIK patients. Mean deviation from intended correction was -0.82 +/- 0.89 D after PRK and +0.19 +/- 0.47 D after LASIK at 1 month (P < .01); +0.16 D +/- 0.37 D after PRK and +0.29 +/- 0.51 D after LASIK at 6 months (P = .906); +0.20 +/- 0.35 D after PRK and +0.37 +/- 0.44 D after LASIK at 1 year (P = .301). At 1 year, 83.3% of PRK eyes and 61.5% of hyperopic LASIK eyes were within +/- 0.50 D of intended correction (P = 1.0). At 1 year, all eyes in both groups had acuity of 20/40 or better uncorrected, and 47.1% of PRK eyes and 54.5% of LASIK eyes had acuity of 20/20 or better uncorrected (P = 1.0). At last follow-up (minimum, 6 months), 2 eyes in each group had lost 2 lines of best spectacle-correct visual acuity, but none had lost more than 2 lines. All PRK patients experienced significant postoperative pain that required systemic medication. LASIK patients had only minor, transient discomfort. CONCLUSION: LASIK and PRK are of comparable efficacy and safety. However, PRK was associated with significant post-operative pain, an initial and temporary myopic overshoot peaking at 1 month, and stability not occurring before 6 months. LASIK was less painful and was associated with more rapid stability (at 1 month) and a trend toward better uncorrected visual acuity, although not statistically significant.