Outcome and Prognosis Factors of Stage IV Cervical Cancer Patients: A Decade Experience

International audiencePurpose/Objective(s)The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stages IVA) and metastatic CC (i.e., stages IV).Materials/MethodsA retrospective review was conducted, based on all consecutive patients treated for stage IV CC in a comprehensive cancer care center between 2004 and 2017.ResultsSixty-eight patients were included. Performance status (PS) was ≥ 2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph nodes metastases (38.6%), 13 had only distant metastases (29.5%) and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (n=14, 58.3%) +/- a concomitant chemotherapy, or a palliative treatment (n=10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), eleven a primary concomitant chemoradiation (25%), and ten a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stages IVA (95%CI=0.7-33.9), and 10.5% for stages IVB (95%CI=3.7-29.7). In multivariate analysis, PS>1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS>1 and pelvic lymph nodes involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC.ConclusionIn daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies

Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial

International audienceBackgroundSorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres in patients with hepatocellular carcinoma.MethodsSARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90Y-loaded resin microspheres 2–5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442.FindingsBetween Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9–33·6) in the SIRT group and 28·1 months (20·0–35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7–9·9) in the SIRT group versus 9·9 months (8·7–11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94–1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related.InterpretationIn patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments.FundingSirtex Medical Inc