Supplementary Material for: Identification of Responders to Sorafenib in Hepatocellular Carcinoma: Is Tumor Volume Measurement the Way Forward?

Objectives: Early assessment of hepatocellular carcinoma (HCC) response during sorafenib (SO) treatment is challenging, since tumor necrosis, extension and radiological appearance can be inhomogeneous. We evaluated the predictive value of different imaging criteria - such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor density and volume variations - in the early follow-up of SO treatment. Methods: The study included 22 patients. CT images from baseline and 2 months were reviewed to assess response according to RECIST 1.1, mRECIST, EASL, Choi's criteria (decreased tumor density by ≥15%) and arterial-enhancing tumor volume ratio; α-fetoprotein (AFP) variations were expressed as AFP ratio. Results: The response criteria and volume measurements were reproducible (k > 0.80). The overall disease control rate was 40.9% by EASL and mRECIST, and 27.3% by RECIST 1.1; a ≥15% decrease in tumor density was observed in 9 patients (40.9%). The mean volume ratio was 1.73 ± 2.12, the mean AFP ratio 14 ± 37. The 1-year survival rate was 65.9%. Volume ratio was the only predictive factor for survival, with 1-year cumulative survival rates of 90% for volume ratios ≤1.1 and of 45.4% for volume ratios >1.1 (p = 0.04). Conclusions: Tumor volume measurements are reproducible and might provide an early predictive marker of response in HCC patients treated with SO

Supplementary Material for: Mismatch repair deficiency in biliary tract cancer: prognostic implications and correlation with histology.

Introduction: Mismatch repair (MMR) deficiency represents a biomarker and therapeutic target in various neoplasms, but its role in biliary tract cancers (BTCs) remains misunderstood. Methods: MMR status was retrospectively assessed using immunohistochemistry in 163-BTCs patients. We identified MMR proficiency (pMMR)/deficiency (dMMR) according to the loss of MMR proteins (MLH-1, PMS-2, MSH-2, MSH-6). The primary objective of the study was to assess the incidence of dMMR in BTCs; the secondary purpose was to explore its association with prognosis and clinical features. Results: dMMR was recorded in 9 patients and it was strongly associated with mucinous histology (p<0.01). Regarding the prognostic effect, in 122-radically resected patients, disease-free-survival (DFS) resulted significantly shorter in dMMR-patients compared to pMMR-patients (10.7 vs 31.3 months, p = 0.025) and so did nodal status (48.2 vs 15.3 months in N0 vs N+) (p < 0.01). Moreover, dMMR confirmed its prognostic role in terms of DFS at multivariate analysis (p = 0.03), together with nodal status (p = 0.01) and resection margin (p = 0.03). In 103 M+ patients (encompassing 41 metastatic de novo and 62 recurred after surgery patients) there weren’t differences between dMMR and pMMR regarding survival analyses. Discussion/Conclusions: dMMR status is strongly correlated with mucinous histology and represents an independent prognostic factor in terms of disease-relapse in patients with resected BTC

Supplementary Material for: Mismatch repair deficiency in biliary tract cancer: prognostic implications and correlation with histology.

Introduction: Mismatch repair (MMR) deficiency represents a biomarker and therapeutic target in various neoplasms, but its role in biliary tract cancers (BTCs) remains misunderstood. Methods: MMR status was retrospectively assessed using immunohistochemistry in 163-BTCs patients. We identified MMR proficiency (pMMR)/deficiency (dMMR) according to the loss of MMR proteins (MLH-1, PMS-2, MSH-2, MSH-6). The primary objective of the study was to assess the incidence of dMMR in BTCs; the secondary purpose was to explore its association with prognosis and clinical features. Results: dMMR was recorded in 9 patients and it was strongly associated with mucinous histology (p<0.01). Regarding the prognostic effect, in 122-radically resected patients, disease-free-survival (DFS) resulted significantly shorter in dMMR-patients compared to pMMR-patients (10.7 vs 31.3 months, p = 0.025) and so did nodal status (48.2 vs 15.3 months in N0 vs N+) (p < 0.01). Moreover, dMMR confirmed its prognostic role in terms of DFS at multivariate analysis (p = 0.03), together with nodal status (p = 0.01) and resection margin (p = 0.03). In 103 M+ patients (encompassing 41 metastatic de novo and 62 recurred after surgery patients) there weren’t differences between dMMR and pMMR regarding survival analyses. Discussion/Conclusions: dMMR status is strongly correlated with mucinous histology and represents an independent prognostic factor in terms of disease-relapse in patients with resected BTC