Background There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). Older patients are often empirically started on low-dose therapy with the aim to avoid toxicities while maximising clinical efficacy. We aimed to verify whether age impacts on overall survival (OS) and whether a reduced starting dose impacts on OS or toxicity experienced by the elderly. Methods In an international, multicentre cohort study, outcomes for those aged <75 or ≥75 years were determined while accounting for common prognostic factors and demographic characteristics in univariable and multivariable models. Results Five thousand five hundred and ninety-eight patients were recruited; 792 (14.1%) were aged ≥75 years. The elderly were more likely to have larger tumours (>7 cm) (39 vs 33%, p < 0.01) with preserved liver function (67 vs 57.7%) (p < 0.01). No difference in the median OS of those aged ≥75 years and <75 was noted (7.3 months vs 7.2 months; HR 1.00 (95% CI 0.93–1.08), p = 0.97). There was no relationship between starting dose of sorafenib 800 mg vs 400 mg/200 mg and OS between those <75 and ≥75 years. The elderly experienced a similar overall incidence of grade 2–4 sorafenib-related toxicity compared to <75 years (63.5 vs 56.7%, p = 0.11). However, the elderly were more likely to discontinue sorafenib due to toxicity (27.0 vs 21.6%, p < 0.01). This did not vary between different starting doses of sorafenib. Conclusions Clinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.
Background Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non‐steroidal anti‐inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods A prospective multicentre cohort study was delivered by an international, student‐ and trainee‐led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre‐specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non‐selective cyclo‐oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12; P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P < 0·001). Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.
289 Background:The incidence of non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is increasing. The impact of NAFLD on overall survival (OS), treatment response and toxicity in patients with HCC treated with sorafenib is unknown. We examined the impact of NAFLD on OS and toxicity in an international cohort of patients receiving sorafenib. Methods:Clinical and demographic data were collected from patients consecutively treated at specialist centres in Europe and North America. The impact of NAFLD on OS, sorafenib-specific survival and sorafenib-related toxicity compared to other aetiologies of liver disease using multivariable Cox-proportional hazards and logistic regression modelling was assessed. Results:5201 patients were treated with sorafenib; 183 (3.6%) had NAFLD-associated HCC. NAFLD-associated HCC patients were more likely to be older women(median age 65.8 vs 63.0 years, p < 0.01 and 10.4% vs 2.3%, < 0.01), with a median BMI of 29.4. After controlling for known prognostic factors, no difference in OS in patients with or without NAFLD was observed(adjusted HR 0.94 (95% CI 0.76 -1.16), p = 0.57). NAFLD-associated patients had more advanced stage HCC when they commenced sorafenib (BCLC C/D 70.9% vs 58.9%, p < 0.01) and were more likely to be commenced on a lower starting dose of sorafenib (51.4 vs. 36.4%, p < 0.01). However, there was no difference in sorafenib-specific survival between NAFLD and other aetiologies(HR 0.99, 95% CI (0.85 – 1.16, p=0.92). Adverse events were similar between NAFLD and non-NAFLD HCC groups, including rates of ≥ grade 2 hypertension(6.3 vs. 5.8%, p = 1.00). A lower rate of severe hand foot syndrome was observed in the NAFLD population(3.8 vs. 12.4%, p = 0.03). Conclusions: OS in HCC does not appear to be influenced by the presence of NAFLD. NAFLD-associated HCC derive similar clinical benefit from sorafenib compared to other aetiologies.
Background & Aims Survival in hepatocellular carcinoma (HCC) is associated with several factors. Our aim was to develop and validate an HCC survival prediction score (HCC‐SPS) based on common clinical parameters and excluding the subsequent therapy received, which would be able to prognosticate all patients with HCC at the time of diagnosis. Methods The development cohort comprised 1270 patients with HCC seen in our department since January 1988. Univariate analysis was performed for known HCC prognostic parameters. Parameters with P < .1 on univariate analysis were then included in a Cox regression with backward model selection. The HCC‐SPS was derived based on the coefficients estimated by Cox regression with selected parameters. The derived HCC‐SPS was then validated with 2 independent international cohorts of 220 patients from the United Kingdom and 90 patients from Hong Kong (HK). Points were allocated to the following variables: ALBI grade, AFP level, portal vein invasion, ECOG status and TNM stage. Results The total score classified a patient into 3 distinct survival risk categories of low, medium and high risk with median survival (weeks) of 249 (95% CI 195–303), 45 (95% CI 38–52) and 9 (95% CI 8–10) respectively. The scoring system was validated by the cohorts from United Kingdom and HK. Conclusions We have formulated an HCC survival prediction score using readily available clinical parameters to risk stratify all HCC patients into distinct survival categories at the time of HCC diagnosis regardless of subsequent treatment received. The score was validated with other independent international cohorts of patients.
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