Influence of cirrhosis on outcomes of patients with advanced intrahepatic cholangiocarcinoma receiving chemotherapy

International audienceBackground: Cirrhosis is a risk factor for intrahepatic cholangiocarcinoma (iCC). However, its exact prevalence is uncertain and its impact on the management of advanced disease is not established.Methods: Retrospective analysis of patients treated with systemic chemotherapy for advanced iCC in the 1st-line setting at 2 tertiary cancer referral centres. Cirrhosis was diagnosed based on at least one element prior to any treatment: pathological diagnosis, baseline platelets <150 × 109/L, portal hypertension and/or dysmorphic liver on imaging.Results: In the cohort of patients (n = 287), 82 (28.6%) had cirrhosis (45 based on pathological diagnosis). Patients with cirrhosis experienced more grade 3/4 haematologic toxicity (44% vs 22%, respectively, P = 0.001), and more grade 3/4 non-haematologic toxicity (34% vs 14%, respectively, P = 0.001) than those without. The overall survival (OS) was significantly shorter in patients with cirrhosis: median 9.1 vs 13.1 months for those without (HR = 1.56 [95% CI: 1.19-2.05]); P = 0.002), confirmed on multivariable analysis (HR = 1.48 [95% CI: 1.04-2.60]; P = 0.028).Conclusion: Cirrhosis was relatively common in patients with advanced iCC and was associated with increased chemotherapy-induced toxicity and shorter OS. Formal assessment and consideration of cirrhosis in therapeutic management is recommended

Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design

Hepatocellular carcinoma in elderly patients: challenges and solutions

International audienceHepatocellular carcinoma (HCC) is the second most common cause of death by cancer in the world. Due to the delayed HCC development in hepatitis C carriers and nonalcoholic fatty liver disease, the incidence of HCC in the elderly is increasing and is becoming a global health issue. Elderly patients with HCC should be assessed through proper oncologic approach, namely, screening tools for frailty (Geriatric-8 or Vulnerable Elders Survey-13) and comprehensive geriatric assessment. This review of the literature supports the same treatment options for elderly patients as for younger patients, in elderly patients selected as fit following proper oncogeriatric assessment. Unfit patients should be managed through a multidisciplinary team involving both oncological and geriatrician professionals. Specific studies and recommendations for HCC in the elderly should be encouraged

Gemcitabine as second-line chemotherapy after Folfirinox failure in advanced pancreatic adenocarcinoma: A retrospective study

International audienceBACKGROUND: Pancreatic adenocarcinoma (PA) is diagnosed in most cases at an advanced stage requiring chemotherapy. Folfirinox is the standard first-line treatment. After Folfirinox failure, gemcitabine alone is routinely used as second-line therapy without data supporting this attitude.AIM: Determine the response rate and outcome of patients with advanced PA treated with gemcitabine after Folfirinox failure.METHODS: We retrospectively analyzed all consecutive patients treated with gemcitabine after Folfirinox failure for a locally advanced or metastatic PA between 2009 and 2015. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Response rate, control rate and tolerability were assessed.RESULTS: 96 patients were included (male, 51%; median age, 62; performance status (PS) 0-1, 47%). Median duration on gemcitabine was 2.1 months. The overall disease control rate was 40%. Median OS was 3.7 months (95%CI: 2.5-5.2) and median PFS was 2.1 months (95%CI: 2.0-2.6). Reasons for treatment discontinuation were mostly progression (51%). Age at diagnosis and PS were independently associated with OS in multivariate analysis (HR of 1.86; p=0.0055 and 2.42; p<0.0001 respectively). 34 patients experienced a grade 3 adverse event.CONCLUSIONS: This study suggests that gemcitabine is not beneficial to all patients failing on Folfirinox first-line therapy and should be restricted to young patients with good PS

Biomarqueurs prédictifs de réponse aux inhibiteurs de points de contrôle immuns

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Influence of cirrhosis on outcomes of patients with advanced intrahepatic cholangiocarcinoma receiving chemotherapy

International audienceBackground: Cirrhosis is a risk factor for intrahepatic cholangiocarcinoma (iCC). However, its impact on the management of advanced disease is not established. Methods: Retrospective analysis of patients (pts) treated with systemic chemotherapy for advanced iCC in the first-line setting at 2 tertiary cancer referral centers, the second center used to validate findings from the first. Cirrhosis was diagnosed based on at least one element among pathological diagnosis, baseline platelet &lt; 150 G/L, portal hypertension and/or dysmorphic liver at imaging. Results: In the first center (n=185), 55 pts (29.7%) had cirrhosis (74.5 % based on pathological diagnosis). Main aetiology of cirrhosis was alcohol for 17 pts (31%), non-alcoolic steato-hepatitis (NASH) for 10 pts (18.2%), and mixed alcohol and NASH for 9 pts (16.4%). 102 (57.0%) pts received gemcitabine-cisplatin, 55 (30.7%) pts received gemcitabine-oxaliplatin, and 11 (6%) pts received gemcitabine, with no difference between cirrhotic and non-cirrhotic pts (p=0.38). Second-line treatment was less frequent in cirrhotic pts (21.8% vs. 50.0%, p=0.001). Cirrhotic pts experienced more grade 3/4 hematologic toxicity than non-cirrhotic pts (38% vs. 20%, respectively, p=0,014), and more grade 3/4 non-hematologic toxicity (28% vs. 15%, respectively, p=0.048). The overall survival (OS) was significantly shorter in cirrhotic pts; median: 9.0 vs. 13.8 months for non-cirrhotic pts (HR = 1.54 [95%CI: 1.09-2.16]; p = 0.014); confirmed on multivariable analysis, adjusted on ALBI-score, ECOG PS, extension of the disease (liver only disease and bilobar) (HR = 1.53 [95% CI: 1.01-2.33]; p=0.046). However, PFS was not significantly shorter in cirrhotic pts: median 9,9 months vs. 11.7 for non-cirrhotics (p = 0.35). In the second center (n=102), similar results were seen: 27 (26.5%) pts had cirrhosis. The cirrhotic pts experienced more grade 3/4 hematologic toxicities than non-cirrhotic pts (55.6% vs. 25.4%, respectively, p=0.005), and more grade 3/4 non-hematologic toxicity (44.4% vs. 12.7%, respectively, p = 0.001). OS was shorter in cirrhotic pts; median 9.1 months vs. 11.7 months for non-cirrhotic pts (HR = 1.81 [95%CI: 1.14-2.87]; p = 0.011). PFS was not significantly shorter in cirrhotic pts: 7.5 months for patients without cirrhosis, and 4.2 months for pts with cirrhosis (p=0.221). Conclusions: Cirrhosis was frequent in pts with advanced iCC, and had a negative impact on patients’ outcomes, with increased chemotherapy-induced toxicity and shorter OS. Formal assessment and consideration of cirrhosis in the therapeutic management should be recommended and could lead to a dose adjustment

Sorafenib use in elderly patients with hepatocellular carcinoma: caution about use of platelet aggregation inhibitors

International audiencePURPOSE: Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). The peak incidence of HCC is around 70 years. We aimed to evaluate safety and efficacy of sorafenib in the elderly population. METHODS: We retrospectively reviewed data from patients treated with sorafenib for HCC at our institution. We compared safety and efficacy data across different age groups. RESULTS: Since 2005, 129 patients were treated, 78 (60.5 %) were \textless70 years old and 51 (39.5 %) were ≥70. The frequency of dose reduction was similar between the two groups (48.7 vs. 58.8 %), as was the occurrence of severe toxicities (41.0 vs. 51.0 %) and hospitalization due to toxicity (9.0 vs. 13.7 %). However, asthenia and bleeding were more frequent in the elderly. The higher frequency of bleeding was explained by concomitant antiplatelet treatments, and major asthenia was frequent in PS1 elderly patients. There was a trend toward less frequent interruption of treatment in the younger group (25.6 vs. 39.2 %) and significantly less frequent definitive discontinuation of treatment due to toxicity (24.4 vs. 45.1 %). Median progression-free survival was 5.6 months in both age groups, while median overall survival was 9.6 months in the younger age group and 12.6 months in the older age group. CONCLUSION: Sorafenib showed similar results in terms of safety and efficacy in the elderly and younger HCC populations. Careful baseline evaluation is needed for patient's selection in the elderly population, including discussion about antiplatelet therapy discontinuation and caution in PS1 patients, as well as active management of toxicity

Occupational radiation exposure of medical staff performing (90)Y-loaded microsphere radioembolization

International audiencePURPOSE: Radioembolization of liver cancer with (90)Y-loaded microspheres is increasingly used but data regarding hospital staff exposure are scarce. We evaluated the radiation exposure of medical staff while preparing and injecting (90)Y-loaded glass and resin microspheres especially in view of the increasing use of these products. METHODS: Exposure of the chest and finger of the radiopharmacist, nuclear medicine physician and interventional radiologist during preparation and injection of 78 glass microsphere preparations and 16 resin microsphere preparations was monitored. Electronic dosimeters were used to measure chest exposure and ring dosimeters were used to measure finger exposure. RESULTS: Chest exposure was very low for both products used (\textless10 μSv from preparation and injection). In our experience, finger exposure was significantly lower than the annual limit of 500 mSv for both products. With glass microspheres, the mean finger exposure was 13.7 ± 5.2 μSv/GBq for the radiopharmacist, and initially 17.9 ± 5.4 μSv/GBq for the nuclear medicine physician reducing to 13.97 ± 7.9 μSv/GBq with increasing experience. With resin microspheres, finger exposure was more significant: mean finger exposure for the radiopharmacist was 295.1 ± 271.9 μSv/GBq but with a reduction with increasing experience to 97.5 ± 35.2 μSv/GBq for the six most recent dose preparations. For administration of resin microspheres, the greatest mean finger exposure for the nuclear medicine physician (the most exposed operator) was 235.5 ± 156 μSv/GBq. CONCLUSION: Medical staff performing (90)Y-loaded microsphere radioembolization procedures are exposed to safe levels of radiation. Exposure is lower than that from treatments using (131)I-lipiodol. The lowest finger exposure is from glass microspheres. With resin microspheres finger exposure is acceptable but could be optimized in accordance with the ALARA principle, and especially in view of the increasing use of radioembolizatio

Yttrium-90 glass microspheres radioembolization (RE) for biliary tract cancer a large single-center experience

International audiencePurpose - Radioembolization (RE) is a promising treatment option for biliary tract cancers (BTC). We report here the largest series to date using this treatment modality. Methods - We retrospectively studied data from 64 patients treated outside prospective clinical trial at our institution. We studied baseline characteristics as potential prognostic factors. We studied dose delivered to the tumor as predictive factors of outcomes in patients not receiving concomitant chemotherapy. Results - The Progression-Free Survival and Overall Survival (OS) were 7.6 months [95% Confidence Interval (CI): 4.6-10.6] and 16.4 months [95% CI: 7.8-25.0] in the whole cohort. The factors independently associated with OS in multivariable analysis were the primary localization of ICC (HR = 0.27, 95% CI: 0.11-0.68, p = 0.005) and a PS > 0 (HR = 2.21, 95% CI: 1.11-4.38, p = 0.024). During follow-up, 12 patients (19%) underwent surgery following downstaging, with a median OS of 51.9 months. In patients not treated with concomitant chemotherapy (n = 31), OS was significantly higher in patients with a dose delivered to the tumor 260Gy or higher than in patients with a dose delivered to the tumor lower than 260Gy (median 28.2 vs 11.4 months, log-rank p = 0.019). Conclusion - Our results confirm that RE is a promising treatment modality in BTC. A high proportion of patients could be downstaged to surgery, with promising long-term survival. Dose delivered to the tumor correlated with clinical outcomes when chemotherapy was not used concomitantly