Protocol of trans-Tasman feasibility randomised controlled trial of the Younger Women's Wellness After Breast Cancer (YWWACP) lifestyle intervention.

BACKGROUND: Younger women (defined as those < 50 years who are likely pre-menopausal at time of diagnosis) with breast cancer often experience persistent treatment-related side effects that adversely affect their physical and psychological wellbeing. The Women's Wellness After Cancer Program (WWACP) was adapted and piloted in Australia to address these outcomes in younger women. The aims of this feasibility study are to determine (1) the potential to translate the Younger WWACP (YWWACP) intervention to a broader population base in Aotearoa/New Zealand and Australia, and (2) the potential for success of a larger, international, phase ΙΙΙ, randomised controlled trial. METHODS: This bi-national, randomised, single-blinded controlled trial involves two main study sites in Aotearoa/New Zealand (Kowhai study) and Australia (EMERALD study). Young women aged 18 to 50 years who completed intensive treatment (surgery, chemotherapy, and/or radiotherapy) for breast cancer in the previous 24 months are eligible. The potential to translate the YWWACP to women in these two populations will be assessed according to several feasibility outcomes. These include examining intervention accessibility, acceptability and uptake; intervention sustainability and adherence; the prevalence components of the intervention in the control group; intervention efficacy; participants' perception of measurement burden; the effectiveness of planned recruitment strategies; and trial methods and procedures. The studies collectively aim to enrol 60 participants in the intervention group and 60 participants in the control group (total = 120 participants). DISCUSSION: Ethical approval has been received from the Southern Health and Disability Ethics Committee (Kowhai ref: 19/STH/215), and UnitingCare Human Research Ethics Committee (EMERALD ref: 202103). This study will provide important data on the feasibility of the refined YWWACP in the trans-Tasman context. This study will account for and harmonise cross-country differences to ensure the success of a proposed international grant application for a phase ΙΙΙ randomised controlled trial of this program to improve outcomes in younger women living with breast cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): Kowhai ACTRN12620000260921 , registered on 27 February 2020. EMERALD ACTRN12621000447853 , registered on 19 April 2021.

Sarcopenia and myosteatosis in patients undergoing curative radiotherapy for head and neck cancer: Impact on survival, treatment completion, hospital admission and cost.

BACKGROUND: Computed tomography (CT) is the gold standard of body composition analysis at the tissue-organ level. The present study aimed to determine the impact of CT-defined sarcopenia and myosteatosis on outcomes, including overall survival, unplanned hospital admissions and related costs, in patients who had completed treatment of curative intent for head and neck cancer (HNC). METHODS: Retrospective observational study of patients undergoing radiotherapy of curative intent ± other treatment modalities for HNC. Tissue density data derived at the third lumbar vertebra (L3) were evaluated with sarcopenia defined per sex-specific published threshold values for skeletal muscle index, stratified by body mass index and mean skeletal muscle attenuation in HU (Hounsfield units). RESULTS: Pre- or post-treatment images were available for 79/98 patients (80.6%) and 61/98 patients (62.2%), respectively. Sarcopenia was present in 42/79 patients pre-treatment and 36/61 patients post-treatment, whereas myosteatosis was present in 63/79 patients pre-treatment and 48/61 patients post-treatment. In patients with pre- and post-treatment images (n = 60), the median (range) percentage weight change was -8.5% (-29.9 to +11.7). On multivariable analysis, a post-treatment sarcopenia hazard ratio of 3.87 (95% confidence interval = 1.22-12.24, P = 0.021) and a pre-treatment myosteatosis hazard ratio of 8.86 (95% confidence interval = 1.12-69.88, P = 0.038) were independent predictors of reduced overall survival. There was no difference in radiotherapy or chemotherapy treatment completion based on pre-treatment sarcopenia status. The mean (SD) difference unplanned hospital admission cost was $15 846 ($17 707) for patients without sarcopenia versus $47 945 ($82 688) for patients with sarcopenia at any time point (P = 0.077). CONCLUSIONS: As CT-defined sarcopenia and myosteatosis hold clinically meaningful prognostic value, muscle status evaluation is recommended in routine clinical practice.

The impact of coronary angiography on renal transplant function.

INTRODUCTION: There may be reluctance to perform coronary angiography in kidney transplant patients due to perceived risk of iodinated contrast, despite an increased risk of cardiovascular disease compared with the general population. AIM: We sought to determine if renal transplant function was adversely affected within 7, 30 and 180 days of coronary angiography. DESIGN AND METHODS: Renal transplant recipients undergoing coronary angiography in a single centre (01/2006-02/2018) were identified retrospectively. Baseline and highest SCr within 7, 30 and 180 days of coronary angiography were extracted from the electronic patient record. Rise in creatinine >26 micromol/l was considered significant [equivalent to Acute Kidney Injury (AKI) Network criteria stage 1 AKI] and case note review performed to determine circumstance of renal decline. RESULTS: There were 127 coronary angiographies conducted in 90 patients: 67.7% were male and mean age was 58.0 (±10.1) years. There was AKI within 7 days in 18.9% cases, but SCr returned to baseline within 7 days or there was an alternative explanation for AKI in 83.3% of these. In the remaining four cases, there was progressive decline in renal transplant function. In the absence of critical illness, no patient required dialysis or extended hospital stay for contrast-associated AKI. CONCLUSIONS: In this cohort of renal transplant recipients undergoing coronary angiography, AKI occurred in a minority of cases, and in more than 95% of such cases this effect was transient, with progressive renal decline a rare and predictable event. Renal transplant should not be regarded as a contraindication to coronary angiography.

High CYP2C19 phenotypic variability in gastrointestinal cancer patients.

PURPOSE: CYP2C19 contributes to the metabolism of several chemotherapeutic agents. The CYP2C19 homozygous null function genotype strongly predicts activity phenotype in healthy populations. An additional acquired loss of function has been reported in up to one-third of cancer patients. It is not known whether this phenomenon also occurs in patients with earlier stage or in resected disease. METHODS: This study investigated whether acquired loss of CYP2C19 function was detectable in patients with stage III-IV or resected gastrointestinal cancer. CYP2C19 genotype was determined in 49 patients, and subjects were probed for CYP2C19 activity on three test occasions. RESULTS: An acquired loss of CYP2C19 activity was observed in 20% of stage III-IV and 17% of resected patients at the first test. Significant (p < 0.01) genotype-phenotype discordance was observed in both groups. There were no direct associations between this discordance and inflammatory markers, tumour burden or chemotherapeutic history. Notably, hepatic CYP2C19 function was not stable over time and phenotype conversion occurred in 23 patients over the period of testing. CONCLUSION: Reliance on germ-line genotype to infer a poor metaboliser status could substantially underestimate the number of patients with deficient CYP2C19 function. This could compromise the interpretation of genotype-based clinical association studies.

A randomised phase IIb trial to assess the efficacy of ReCharge ice cream in preventing chemotherapy-induced diarrhoea.

PURPOSE: Chemotherapy-induced diarrhoea (CID) has a significant impact. A medicinal food product (ReCharge) containing iron-saturated lactoferrin and anhydrous milk fat reduces the detrimental effects of chemotherapy on the gut in animals. We report results of a randomised blinded placebo-controlled phase IIb trial investigating the efficacy and safety of ReCharge in preventing CID. METHODS: Eligible patients were adults due to start the first cycle of a 2- or 3-week-cycle chemotherapy regimen, had an Eastern Cooperative Oncology Group (ECOG) status of 3 or less, had adequate haematological, liver and renal function and provided written informed consent. Patients (197) were randomised to ReCharge or placebo. They consumed 100-g study product for 2 weeks before and 6 weeks after starting chemotherapy, completed daily diaries for 8 weeks and attended clinic visits until 12 weeks (2-week cycles) or 14 weeks (3-week cycles). The primary outcome was days with CID. RESULTS: The mean number of days with diary-recorded CID was marginally but not statistically significantly lower on ReCharge than placebo (-2.0, 95 % CI (-4.7 to 0.7), p = 0.2). The proportion reporting diarrhoea in the previous cycle at the clinic visit was 30 % lower (p = 0.012) on ReCharge. Missing diary data may have contributed to the discrepancy. No significant differences were found in quality of life or other adverse events. CONCLUSIONS: We found no clear evidence that ReCharge reduced CID as measured by patient self-report diary. The converse finding of benefit as recorded at clinic visits and incomplete adherence to diary completion indicates that further research is required into methods for measuring CID.

A randomized 'N-of-1' single blinded clinical trial of barbed dermal sutures vs. smooth sutures in elective plastic surgery shows differences in scar appearance two-years post-operatively.

BACKGROUND: Barbed sutures have unidirectional circumferential shallow barbs, which distribute tension throughout the wound and close wound securely without the need to tie knots. OBJECTIVES: We compare two different methods of wound closure in elective plastic surgical cases: barbed 3/0 V-Loc™180 suture and smooth 3/0 Maxon™ sutures, both polyglyconate monofilament synthetic absorbable sutures. We assessed the aesthetic long-term results with a minimum two year follow up. METHODS: This is a prospective, randomized controlled study with internal control. A single surgeon performed all cases. Patients who underwent elective operations that involved long wound closure were enrolled in the study. Each patient acted as their own internal control with half their wound being sutured with 3/0 V-Loc™180 barbed suture and the other half with smooth 3/0 Maxon™ deep dermal sutures and then a subcuticular skin closure. In both groups, the superficial fascial system was closed with 1 Vicryl interrupted sutures on both sides. Long-term cosmesis was evaluated using the modified Hollander cosmesis score by review of standardized postoperative photographs by 9 blinded plastic surgeons and specialist registrars. RESULTS: The study reports on 33 female patients. The time taken for wound closure was significantly reduced using the barbed suture (p < 0.001). There was no difference in the complication ratio in either group. Two-year aesthetic outcome was significantly superior when using the barbed suture (p = 0.0075). CONCLUSION: Barbed sutures closure of long wounds is faster and produces a better long-term aesthetic outcome than smooth sutures.

A randomized phase II study comparing capecitabine alone with capecitabine and oral cyclophosphamide in patients with advanced breast cancer-cyclox II.

BACKGROUND: Capecitabine and cyclophosphamide are active in patients with advanced breast cancer, have non-overlapping toxic effects and synergy pre-clinically. We explored the efficacy and toxic effect of an all-oral combination of capecitabine with cyclophosphamide versus capecitabine alone in a multicentre, randomized, phase II study. PATIENTS AND METHODS: Patients with locally advanced or metastatic breast cancer were randomized to treatment with capecitabine given continuously (666 mg/m(2) b.i.d. days 1-28) alone (C) or with oral cyclophosphamide (100 mg/m(2) days 1-14 of a 28-day cycle) (CCy) for up to six cycles. RESULTS: Eighty-two patients were randomized. There was no complete response. The proportions with partial response were 36% on C and 44% on CCy, a difference of 7.9% [95% confidence interval (CI) -13.4 to 29.1]. Significant toxic effect was uncommon: grade ≥3 diarrhoea in 4 (10%) versus 1 (3%) patients; grade ≥3 fatigue in 2 (5%) versus 5 patients (13%) and grade ≥2 hand-foot syndrome in 7 (17%) versus 11 (28%) patients receiving C versus CCy, respectively. Median progression-free survival was 3.1 months on C and 6.9 months on CCy, not significantly different statistically. There was no difference in overall survival. CONCLUSION: The difference in tumour response suggests a reasonable chance that CCy is superior to C alone.

Using a wiki platform to promote guidelines internationally and maintain their currency: evidence-based guidelines for the nutritional management of adult patients with head and neck cancer.

BACKGROUND: The present study describes the development of evidence-based practice guidelines for the nutritional management of adult patients with head and neck cancer using a wiki platform to enable wide international stakeholder consultation and maintain currency. METHODS: A dietitian steering committee and a multidisciplinary steering committee were established for consultation. Traditional methods of evidence-based guideline development were utilised to perform the literature review, assess the evidence and produce a draft document. This was transferred to a wiki platform for stakeholder consultation and international endorsement processes in Australia, New Zealand and the UK. Data were collected on website traffic utilising Google Analytics. RESULTS: In addition to broad stakeholder consultation through the steering committees, an additional twenty comments were received via the wiki by twelve individuals covering six different professions from three different countries, compared to four comments by e-mail. The guidelines were subsequently endorsed by the dietetic associations of Australia, New Zealand and the UK. During a 4-month period monitoring the use of the guidelines, there were 2303 page views to the landing page from 33 countries. The average number of pages accessed per visit was five and the duration of time spent on the website was approximately 6 min. CONCLUSIONS: Using a wiki platform for guideline development and dissemination is a successful method for producing high-quality resources that can undergo wide international stakeholder review and include open public consultation. This can replace conventional methods whereby guidelines can quickly become outdated.

Comparing breast-reduction techniques: time-to-event analysis and recommendations.

BACKGROUND: Breast reduction is a common procedure used to improve physical and aesthetic factors associated with breast hypertrophy. This study investigated how surgical technique alone affects the risk factors for complications and profiled differences between techniques. Complications were assessed by the use of time-to-event methods. METHODS: Patient information was extracted from a cohort of 283 patients. Demographic, surgical, and follow-up information was analyzed for patients undergoing surgical procedures using the inferior pedicle Wise pattern (IPWP) and modified Hall-Findlay (MHF) techniques. The patients managed with the IPWP technique were considered control subjects. The failure rates were described using the Kaplan-Meier failure estimator to provide a true estimate of the experienced complication rates. RESULTS: Overall, few differences were noted between the groups except for total tissue removed. The overall failure (complication) rate at 6 months was 18.8%, with 9% of all the patients experiencing a major complication that required operative intervention/revision. As expected, the period with the greatest risk of complication was the first month after surgery. Surgical technique, total tissue removed, and age were nonpredictive of complications. Overall, the IPWP group had significantly more total tissue removed than the MHF group (median difference, 227 g; P=0.002). There was no evidence of a learning curve when an experienced surgeon moved from the one technique to the other. CONCLUSION: At 6 months after surgery, 19% of patients are expected to have experienced a complication. There appears to be few differences in outcomes between the techniques of breast reductions used, and the success or otherwise almost certainly relates to factors independent of surgical technique and includes patient selection, operative skill, and experience. Time-to-event analysis provides a precise assessment and description of the complication profile. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC. METHODS: From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day(-1)). End points were overall survival (OS) and quality of life. RESULTS: An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92-1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting. CONCLUSION: Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

Minimally invasive late free flap salvage: indications, efficacy and implications for reconstructive microsurgeons.

One of the most common causes of free flap compromise is microvascular thrombosis. Acland et al describe two described zones of injury: zone 1 the anastomotic site and zone 2 downstream. Factors contributing to zone 1 thromboses include anastomotic irregularities, suture material and platelet adhesion. This often presents in the early postoperative period. Zone 2 however, is less well described and is associated with diffuse microvascular ischaemia. Often, these cases are associated with the use of vein grafts in a delayed reconstructive setting, and present relatively late in their postoperative follow up. There are sporadic reports in the literature of late free flap salvage managed via anastomotic revision, thrombectomy, and the use of thrombolytic agents. We describe the successful use of catheter-directed endovascular urokinase in revascularizing two free flaps which presented in the late postoperative setting. This report demonstrates the safety and efficacy of this technique in free flap salvage. Although late presentation of free flap compromise is uncommon, this report reiterates the importance of long-term surveillance of these patients. It should be remembered, however, that long-term anticoagulation is required, and may not be feasible in certain patient populations. Given that free tissue transfer is often employed when other forms of reconstruction are unavailable, endovascular thrombolysis is a valuable tool for the reconstructive microsurgeon, and its role in early free flap salvage warrants exploration.

Chemotherapy-induced reversible posterior leucoencephalopathy syndrome.

Reversible posterior leucoencephalopathy syndrome is a neurological condition seen in various areas of acute medicine, including the administration of antineoplastic therapies used in haemato-oncology patients. It is a rare complication that has been increasingly recognized. It is characterized by altered mental status, visual disturbance, headache and seizures. Magnetic resonance imaging typically shows vasogenic oedema in the posterior regions of the brain. Although its name suggests reversibility, it may result in an irreversible brain injury without prompt treatment. Therefore, it is vital for treating clinicians to recognize this syndrome. We describe the case of a 55-year-old woman with advanced pancreatic adenocarcinoma, who developed clinical and radiological manifestations consistent with this syndrome as a complication of gemcitabine monotherapy.

CYP2C19 pharmacogenetics in advanced cancer: compromised function independent of genotype.

CYP2C19 is a drug-metabolising enzyme involved in the metabolism of a number of chemotherapeutic agents including cyclophosphamide. Variants of the CYP2C19 gene result in a loss of function polymorphism, which affects approximately 3% of the Caucasian population. These individuals are poor metabolisers (PM) of a wide range of medications including omeprazole (OMP). In healthy subjects PM can be identified through homozygous variant genotype. However, a discordance between CYP2C19 genotype and phenotype has been reported previously in a small study of cancer patients. To investigate whether CYP2C19 activity was decreased in patients with advanced cancer, CYP2C19 genotype was determined in 33 advanced cancer patients using PCR-RFLP analysis for the two important allelic variants (*2,681G>A and *3,636G>A) and the activity of the enzyme was evaluated using the CYP2C19 probe drug OMP. The activity of the drug-metabolising enzyme CYP2C19 was severely compromised in advanced cancer patients, resulting in a PM status in 37% of the patients who had normal genotype. This is significantly (P<0.0005) higher than that would be predicted from the genotypic status of these patients. There was no evidence of a correlation between compromised CYP2C19 activity and any of the proinflammatory cytokines or acute phase response proteins studied. However, there was preliminary evidence of an association between PM status and low body mass (P=0.03). There is increasing interest in using pharmacogenetics to 'individualise medicine', however, the results of this study indicate that in a cancer population genotyping for CYP2C19 would significantly underestimate the number of phenotypic PM of drugs, such as cyclophosphamide, which may be metabolised by this enzyme.

Myogel, a novel, basement membrane-rich, extracellular matrix derived from skeletal muscle, is highly adipogenic in vivo and in vitro.

BACKGROUND/AIMS: Biological and synthetic scaffolds play important roles in tissue engineering and are being developed towards human clinical applications. Based on previous work from our laboratory, we propose that extracellular matrices from skeletal muscle could be developed for adipose tissue engineering. METHODS: Extracellular matrices (Myogels) extracted from skeletal muscle of various species were assessed using biochemical assays including ELISA and Western blotting. Biofunctionality was assessed using an in vitro differentiation assay and a tissue engineering construct model in the rat. RESULTS: Myogels were successfully extracted from mice, rats, pigs and humans. Myogels contained significant levels of laminin alpha4- and alpha2-subunits and collagen I compared to Matrigel, which contains laminin 1 (alpha1beta1gamma1) and collagen IV. Levels of growth factors such as fibroblast growth factor 2 were significantly higher than Matrigel, vascular endothelial growth factor-A levels were significantly lower and all other growth factors were comparable. Myogels reproducibly stimulated adipogenic differentiation of preadipocytes in vitro and the growth of adipose tissue in the rat. CONCLUSIONS: We found Myogel induces adipocyte differentiation in vitroand shows strong adipogenic potential in vivo, inducing the growth of well-vascularised adipose tissue. Myogel offers an alternative for current support scaffolds in adipose tissue engineering, allowing the scaling up of animal models towards clinical adipose tissue engineering applications.

Effective oral chemotherapy for breast cancer: pillars of strength.

Traditionally, anticancer therapy has been dominated by intravenous drug therapy. However, oral agents provide an attractive approach to chemotherapy and use of oral treatments is increasing. We discuss the benefits and challenges of oral chemotherapy from the perspectives of patients, healthcare providers and healthcare funders. Important issues include patient preference, efficacy, compliance, bioavailability, reimbursement, use in special patient populations, financial and staff time savings and flexibility of dosing. We review data for traditional oral agents (e.g. cyclophosphamide, methotrexate), newer oral chemotherapies (e.g. capecitabine), oral formulations of traditionally intravenous agents (e.g. vinorelbine, idarubicin) and new biologic agents under evaluation in breast cancer (e.g. tyrosine kinase inhibitors). Lastly, we review studies of all-oral combination regimens. The wealth of data available and the increasing use of oral agents in breast cancer suggest that many of the concerns and perceptions about oral therapy, including efficacy and bioavailability, have been overcome, and that oral therapy will play a major role in breast cancer management in the future in both the metastatic and adjuvant settings.

Phase II study of carboplatin followed by sequential gemcitabine and paclitaxel as first-line treatment for advanced ovarian cancer.

The aim of this exploratory phase II study was to evaluate sequential chemotherapy with carboplatin followed by gemcitabine-paclitaxel combination in chemonaive patients with advanced ovarian cancer. The primary objective was to evaluate time to progressive disease (TTPD); secondary objectives included the evaluation of 1- and 3-year survival, response rates, and toxicity. Following initial debulking surgery or biopsy, patients with FIGO stage IIC-IV disease received four cycles of carboplatin area under the curve (AUC) 6 (day 1) every 21 days, followed by four cycles of gemcitabine 1000 mg/m(2) (days 1 and 8) and paclitaxel 175 mg/m(2) (day 8) every 21 days. A total of 47 patients enrolled, 44 (93.6%) completed the initial four cycles, and 39 patients (82.9%) completed the planned eight cycles. The median and maximum lengths of follow-up were 31.2 and 43.7 months, respectively. Median TTPD was 13.8 months (95% CI, 11.6-21.0 months), and median survival time was 31.2 months (95% CI, 25.2-39.6 months). Survival at 1 and 3 years was 95.7% and 44.2%, respectively. Of the 43 evaluable patients, most (95.3%) of them achieved a CA-125 marker response based on Gynecologic Cancer Intergroup (GCIG) definition. The partial response rate in the seven patients with measurable disease was 46.4%. Myelosuppression was the major toxicity, with grade 3 and 4 neutropenia observed in 76.6% patients and thrombocytopenia in 12.8% patients. The sequential approach of carboplatin followed by gemcitabine-paclitaxel as first-line treatment for patients with ovarian cancer is feasible and well tolerated, and depending upon the findings from other major trials, it may merit further evaluation.

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.