Subgroup analyses in randomized phase III trials of systemic treatments in patients with advanced solid tumours: a systematic review of trials published between 2017 and 2020.

BACKGROUND: Subgroup analyses of randomized controlled trials are very common in oncology; nevertheless, the methodological approach has not been systematically evaluated. The present analysis was conducted with the aim of describing the prevalence and methodological characteristics of the subgroup analyses in randomized controlled trials in patients with advanced cancer. METHODS: A systematic literature search using PubMed was carried out to identify all phase III randomized controlled trials conducted in adult patients affected by locally advanced or metastatic solid tumours, published between 2017 and 2020. RESULTS: Overall, 253 publications were identified. Subgroup analyses were reported in 217 (86%) publications. A statistically significant association of presence of subgroup analysis with study sponsor was observed: subgroup analyses were reported in 157 (94%) for-profit trials compared with 60 (70%) non-profit trials (P < 0.001). Description of the methodology of subgroup analysis was completely lacking in 82 trials (38%), only cited without methodological details in 100 trials (46%) and fully described in 35 trials (16%). Forest plot of subgroup analyses for the primary endpoint was available in 195 publications (77%). Among publications with reported forest plots, the median number of subgroups for primary endpoint was 19 (range 6-78). Out of the 217 publications with subgroup analyses, authors discuss the heterogeneity of treatment effect among different subgroups in 173 publications (80%), although a formal test for interaction for subgroup analysis of primary endpoint was reported for at least one variable only in 60 publications (28%). Correction for multiplicity was explicitly carried out only in nine trials (4%). CONCLUSIONS: The very high prevalence of subgroup analyses in published papers, together with their methodological weaknesses, makes advisable an adequate education about their correct presentation and correct reading. More attention about proper planning and conduction of subgroup analysis should be paid not only by readers, but also by authors, journal editors and reviewers.

Deficiencies in health-related quality-of-life assessment and reporting: a systematic review of oncology randomized phase III trials published between 2012 and 2016.

Quality of life (QoL) is a relevant end point and a topic of growing interest by both scientific community and regulatory authorities. Our aim was to review QoL prevalence as an end point in cancer phase III trials published in major journals and to evaluate QoL reporting deficiencies in terms of under-reporting and delay of publication. All issues published between 2012 and 2016 by 11 major journals were hand-searched for primary publications of phase III trials in adult patients with solid tumors. Information about end points was derived from paper and study protocol, when available. Secondary QoL publications were searched in PubMed. In total, 446 publications were eligible. In 210 (47.1%), QoL was not included among end points. QoL was not an end point in 40.1% of trials in the advanced/metastatic setting, 39.7% of profit trials and 53.6% of non-profit trials. Out of 231 primary publications of trials with QoL as secondary or exploratory end point, QoL results were available in 143 (61.9%). QoL results were absent in 37.6% of publications in the advanced/metastatic setting, in 37.1% of profit trials and 39.3% of non-profit trials. Proportion of trials not including QoL as end point or with missing QoL results was relevant in all tumor types and for all treatment types. Overall, 70 secondary QoL publications were found: for trials without QoL results in the primary publication, probability of secondary publication was 12.5%, 30.9% and 40.3% at 1, 2 and 3 years, respectively. Proportion of trials not reporting QoL results was similar in trials with positive results (36.5%) and with negative results (39.4%), but the probability of secondary publication was higher in positive trials. QoL is not included among end points in a relevant proportion of recently published phase III trials in solid tumors. In addition, QoL results are subject to significant under-reporting and delay in publication.

Percutaneous radiofrequency ablation of hepatocellular carcinoma compared to percutaneous ethanol injection in treatment of cirrhotic patients: an Italian randomized controlled trial.

AIM: To compare 5-year survival of patients with a single hepatocellular carcinoma≤3 cm randomly assigned to receive percutaneous ethanol injection or radiofrequency ablation. PATIENTS AND METHODS: A total of 285 patients (192 males, mean age 70 years), with a single hepatocellular carcinoma (mean diameter 2.2 cm) were randomly assigned to receive percutaneous ethanol injection (n=143) or radiofrequency ablation (n=142). The primary endpoint of the study was 5-year survival. RESULTS: Overall 143 patients underwent percutaneous ethanol injection and 128 radiofrequency ablation. In consideration of segmental location, in fact, 14 patients with 14 hepatocellular carcinomas could not be treated with established radiofrequency and were treated with percutaneous ethanol injection; these patients were not included in the survival evaluation. In the percutaneous ethanol injection and in the radiofrequency ablation groups, 3- and 5-year survival rates of 74% and 68%, and 78% and 68%, and 79% and 70% [corrected] respectively, were observed (p=n.s). In the percutaneous ethanol injection group, 3- and 5-year local recurrence rates were 9.4% and 12.8% respectively; in the radiofrequency group, the 3 and 5 years local recurrence rates were 7.8% and 11.7%, respectively (p=n.s.). The overall costs of percutaneous ethanol injection and radiofrequency ablation were 1359 Euros and 171.000 Euros, respectively (p<0.0001) CONCLUSION: Percutaneous ethanol injection and radiofrequency ablation conferred similar 5-year survival. Feasibility is not the same for both procedures. Percutaneous ethanol injection is much cheaper than radiofrequency ablation and should be considered whether in poor and rich countries.

Radiofrequency ablation of hepatocellular carcinoma extended into the portal vein: Preliminary results.

INTRODUCTION: We report our preliminary results of radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and neoplastic portal thrombus (NPT) in cirrhotic patients. METHODS: Ten patients (7 males and 3 females; mean age 68 yrs) with 10 HCC nodules (37-49 mm) extended into the main portal vein (MPV) underwent RF ablation. Diagnosis of NPT was achieved by fine-needle biopsy. RF ablation was performed firstly on the NPT and then on the HCC. RF ablation was considered successful when complete necrosis of the HCC and complete recanalization of the MPV were achieved. HCC necrosis was evaluated using contrast-enhanced CT. Recanalization of the portal vessels (PV) was analyzed using Color Doppler (CD). RF ablation was performed under ultrasonographic (US) guidance using a perfused electrode needle. RESULTS: Complete necrosis of the HCC with complete recanalization of the PV was observed in 7 patients (success rate: 70%). In the remaining 3, necrosis of the HCC ranged from 70% to 95%, and recanalization of the PV was not complete. No major complications occurred. In 2 cases, mild ascites and increased aspartate aminotransferase/alanine aminotransferase (AST/ALT) values were observed. The follow-up ranged from 4 to 24 months; 1 and 2-year survival rates were 77% and 77%, respectively. At the last follow-up, the 7 successful patients were alive and the portal system was still patent. The 3 unsuccessful patients died within 5 months due to progressive disease. CONCLUSION: RF ablation can destroy HCC and NPT achieving a high rate of efficacy and low rate of complications. However, to confirm these results a control group and a longer follow-up are required.

Clinical and sonographic management of viable hydatid liver cysts.

AIM: The aim of this study was to review our 18-year experience in the treatment of viable hydatid liver cysts (HLCs) with double percutaneous aspiration and ethanol injection (D-PAI) and to provide indications for the clinical management of HLCs. MATERIALS AND METHODS: From January 1989 to December 2007, 127 patients (100 males; 13-80 years) with 184 viable HLCs (137 univesicular, 47 multivesicular; 2.8-20 cm) underwent D-PAI. RESULTS: Ultrasonography (US) showed complete disappearance of 125/184 (68%) cysts; in the remaining 59 cases, an inactive solid (37 cases, 20%) or liquid pattern (22 cases, 12%) was observed with volume decreases of 50-80%. The final US pattern was unmodified during the follow-up in 96.8%. Local recurrences were observed in 5 patients (3.9%): 4 patients with 8 multivesicular cysts and 1 patient with a bilocular cyst (with a solid pattern on US) that ruptured into the biliary tree 2 years after the procedure and disappeared after endoscopic sphincterectomy. The mortality rate was 0.8%, and the overall morbidity was 8.6%. The mean hospital stay was 2.9 days. The time of healing for smaller cysts (<5 cm) was shorter than that of large cysts (≥5 cm) (P < 0.001). CONCLUSION: Our long-term results confirm the high effectiveness of D-PAI in the treatment of HLCs. These results suggest that multilocular cysts require closer follow-up than unilocular cysts.