The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>The GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>A total of 220 patients with HCC treated with either transarterial (<jats:italic>n</jats:italic> = 121) or systemic treatments (<jats:italic>n</jats:italic> = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The GALAD score showed a strong correlation with BCLC stage (<jats:italic>p</jats:italic> < 0.001) and total tumor diameter before treatment (<jats:italic>p</jats:italic> < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (<jats:italic>p</jats:italic> > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (<jats:italic>p</jats:italic> < 0.001).</jats:p> <jats:p>In the transarterial treatment group, the GALAD score (AUC = 0.715; <jats:italic>p</jats:italic> < 0.001) as well as the BALAD score (AUC = 0.696; <jats:italic>p</jats:italic> < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>The GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.</jats:p> </jats:sec&gt

Repeated percutaneous hepatic perfusion with melphalan can maintain long-term response in patients with liver cancers

Chemosaturation (CS; CHEMOSAT®, Delcath Systems Inc.) temporarily administers melphalan into the liver by percutaneous hepatic perfusion (PHP). CS-PHP can effectively control growth in liver tumors, but efficacy and tolerability of sequential treatments are unclear. We analyzed outcomes of sequential CS-PHP treatment. Patients with either unresectable intrahepatic metastases of ocular melanoma (OM, n = 9), cholangiocarcinoma (CCA, n = 3), or hepatocellular carcinoma (HCC, n = 1) were recruited retrospectively. Response was assessed by tomography imaging. Ten patients (mean age 60 years) with more than one CS-PHP treatment were included. CS-PHP was administered 2-6 times in the OM patients, 3 times in the CCA, and the HCC patient received 6 treatments. Overall response rate (ORR) to CS-PHP was 80%, and stable disease was achieved in one patient. Median hepatic progression-free survival (hPFS) was 336 days (range 0-354) for OM, 251 days for the CCA patient, and 256 days for the HCC patient. At the end of observation (153-701 days after first CS-PHP), 6/10 patients were still alive (5/9 with OM, 0 with CCA, and 1 with HCC). Death cases were not related to CS-PHP. Adverse events were mostly hematologic, grade I-IV, and self-resolving. The liver function was not deteriorated by CS-PHP. We conclude that repeated CS-PHP treatments were effective and well tolerated in the long term

Repeated percutaneous hepatic perfusion with melphalan can maintain long-term response in patients with liver cancers

AbstractChemosaturation (CS; CHEMOSAT®, Delcath Systems Inc.) temporarily administers melphalan into the liver by percutaneous hepatic perfusion (PHP). CS-PHP can effectively control growth in liver tumors, but efficacy and tolerability of sequential treatments are unclear. We analyzed outcomes of sequential CS-PHP treatment. Patients with either unresectable intrahepatic metastases of ocular melanoma (OM, n = 9), cholangiocarcinoma (CCA, n = 3), or hepatocellular carcinoma (HCC, n = 1) were recruited retrospectively. Response was assessed by tomography imaging. Ten patients (mean age 60 years) with more than one CS-PHP treatment were included. CS-PHP was administered 2–6 times in the OM patients, 3 times in the CCA, and the HCC patient received 6 treatments. Overall response rate (ORR) to CS-PHP was 80%, and stable disease was achieved in one patient. Median hepatic progression-free survival (hPFS) was 336 days (range 0–354) for OM, 251 days for the CCA patient, and 256 days for the HCC patient. At the end of observation (153–701 days after first CS-PHP), 6/10 patients were still alive (5/9 with OM, 0 with CCA, and 1 with HCC). Death cases were not related to CS-PHP. Adverse events were mostly hematologic, grade I-IV, and self-resolving. The liver function was not deteriorated by CS-PHP. We conclude that repeated CS-PHP treatments were effective and well tolerated in the long term.</jats:p

Dickkopf-Related Protein 1 as Response Marker for Transarterial Chemoembolization of Hepatocellular Carcinomas

Background and Aims: In the treatment of hepatocellular carcinoma (HCC), response prediction to transarterial chemoembolization (TACE) based on serum biomarkers is not established. We have studied the association of circulating Dickkopf-related protein 1 (DKK-1) with baseline characteristics and response to TACE in European HCC patients. Methods: Patients with HCC treated with TACE from 2010 to 2018 at a tertiary referral hospital were retrospectively enrolled. Levels of DKK-1 were measured in serum samples collected before TACE. Response was assessed according to mRECIST criteria at week 12 after TACE. Results: Ninety-seven patients were enrolled, including seventy-nine responders and eighteen refractory. Before TACE, median DKK-1 serum levels were 922 [range, 199–4514] pg/mL. DKK-1 levels were lower in patients with liver cirrhosis (p = 0.002) and showed a strong correlation with total radiologic tumor size (r = 0.593; p < 0.001) and with Barcelona Clinic Liver Cancer stages (p = 0.032). Median DKK-1 levels were significantly higher in refractory patients as compared to responders (1471 pg/mL [range, 546–2492 pg/mL] versus 837 pg/mL [range, 199–4515 pg/mL]; p < 0.001), and DKK-1 could better identify responders than AFP (AUC = 0.798 vs. AUC = 0.679; p < 0.001). A DKK-1 cutoff of ≤1150 pg/mL was defined to identify responders to TACE with a sensitivity of 78% and specificity of 77%. DKK-1 levels were suitable to determine response to TACE in patients with low AFP serum levels (AFP levels < 20 ng/mL; AUC = 0.843; 95% CI [0.721–0.965]; p = 0.003). Conclusion: DKK-1 levels in serum are strongly associated tumor size and with response to TACE in European HCC patients, including those patients with low AFP levels

Dickkopf-Related Protein 1 as Response Marker for Transarterial Chemoembolization of Hepatocellular Carcinomas

Background and Aims: In the treatment of hepatocellular carcinoma (HCC), response prediction to transarterial chemoembolization (TACE) based on serum biomarkers is not established. We have studied the association of circulating Dickkopf-related protein 1 (DKK-1) with baseline characteristics and response to TACE in European HCC patients. Methods: Patients with HCC treated with TACE from 2010 to 2018 at a tertiary referral hospital were retrospectively enrolled. Levels of DKK-1 were measured in serum samples collected before TACE. Response was assessed according to mRECIST criteria at week 12 after TACE. Results: Ninety-seven patients were enrolled, including seventy-nine responders and eighteen refractory. Before TACE, median DKK-1 serum levels were 922 [range, 199&ndash;4514] pg/mL. DKK-1 levels were lower in patients with liver cirrhosis (p = 0.002) and showed a strong correlation with total radiologic tumor size (r = 0.593; p &lt; 0.001) and with Barcelona Clinic Liver Cancer stages (p = 0.032). Median DKK-1 levels were significantly higher in refractory patients as compared to responders (1471 pg/mL [range, 546&ndash;2492 pg/mL] versus 837 pg/mL [range, 199&ndash;4515 pg/mL]; p &lt; 0.001), and DKK-1 could better identify responders than AFP (AUC = 0.798 vs. AUC = 0.679; p &lt; 0.001). A DKK-1 cutoff of &le;1150 pg/mL was defined to identify responders to TACE with a sensitivity of 78% and specificity of 77%. DKK-1 levels were suitable to determine response to TACE in patients with low AFP serum levels (AFP levels &lt; 20 ng/mL; AUC = 0.843; 95% CI [0.721&ndash;0.965]; p = 0.003). Conclusion: DKK-1 levels in serum are strongly associated tumor size and with response to TACE in European HCC patients, including those patients with low AFP levels

Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Protroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT). &lt;b&gt;&lt;i&gt;Patients and Methods:&lt;/i&gt;&lt;/b&gt; Of the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Nine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (&lt;i&gt;n&lt;/i&gt; = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for &amp;#x3e;3 days occurred in &amp;#x3c;15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Application of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.</jats:p