scholarly journals 03:45 PM Abstract No. 213 Synthetic liver function and absolute lymphocyte count are associated with tumor response to locoregional therapy as well as immunosuppressive cell populations in transplant waitlist patients with hepatocellular carcinoma: single-center, prospective, observational trial

2019 ◽  
Vol 30 (3) ◽  
pp. S96
Author(s):  
T. Sandow ◽  
K. Nunez ◽  
J. Gimenez ◽  
V. Ramalingam ◽  
P. Gulotta ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Lymphocyte Count ◽  
Tumor Response ◽  
Absolute Lymphocyte Count ◽  
Locoregional Therapy ◽  
Cell Populations ◽  
Single Center ◽  
Observational Trial ◽  
Immunosuppressive Cell

scholarly journals Radiological Appearance of Hepatocellular Carcinoma Predicts the Response to Trans-arterial Chemoembolization in Patients Undergoing Liver Transplantation

2019 ◽  
Author(s):  
Wei Zhang ◽  
An-Hui Xu ◽  
Wei Wang ◽  
Yan-Hui Wu ◽  
Qian-Ling Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Tumor Necrosis ◽  
Tumor Response ◽  
Locoregional Therapy ◽  
Arterial Phase ◽  
Radiological Appearance ◽  
Explant Analysis ◽  
Complete Tumor ◽  
Arterial Chemoembolization

Abstract Background: The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE. Methods: From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT. Results: Eighty nine TACE procedures (1.35±0.67; 1-4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P=0.002), “typical tumor enhancement” (P=0.010) and smooth tumor margins (p=0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis. Conclusion s : The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.

Safety, tolerability and efficacy of transarterial chemoembolization using anthracyclines-loaded drug eluting microspheres for treatment of patients with unresectable hepatocellular carcinoma: Pooled analyses.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 287-287
Author(s):  
Thierry De Baere ◽  
Filipe Veloso Gomes ◽  
Gontran Verset ◽  
Gerardo Tovar-Felice ◽  
Katerina Malagari ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Transarterial Chemoembolization ◽  
Tumor Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
Close Monitoring ◽  
Bridge To Transplant ◽  
Level Data ◽  
Drug Eluting

287 Background: Transarterial chemoembolization either with Lipiodol (cTACE) or with drug eluting microspheres (DEM-TACE) is indicated for the treatment of hepatocellular carcinoma (HCC) not amenable to curative treatments in patients with preserved liver function. Safety of TACE is becoming more important with its increased use as a bridge to transplant or downstaging to resection, but also for preservation of liver function in case of subsequent immuno-combination therapies. LifePearl microspheres is a novel DEM comprised of polyethylene-glycol with reported good safety profile and efficacy in smaller series. Our purpose was to assess safety and efficacy of TACE using anthracycline loaded LifePearl for the treatment of patients with unresectable HCC in a pooled analysis of studies with available more than 500 patient’s level data. Methods: We pooled patient level data from 5 single arm studies. Safety was assessed by close monitoring of adverse events according to CTCAE (v4.03). Tumor response was assessed, according to mRECIST and RECIST1.1 and analyzed as best overall response to account for differences in time of imaging follow-up between studies. The Kaplan-Meier method was used to estimate event rates for time to event outcomes: progression free survival (PFS), time to unTACEable progression (TTUP) and overall survival (OS) censoring patients at time of surgery or transplantation. Results: Out of 586 patients, 85.5%, 13.5% and 1.0% were Child Pugh A, B and C, respectively. BCLC stages 0, A, B and C were 13.6%, 43.4%, 41.1% and 1.9% respectively. The mean number of HCC lesions was 2.1±1.5 and mean sum of tumor diameters was 49.3±32.9mm. In 19% of patients alpha-feto protein level was > 200ng/ml. A mean of 1.9±1.3 DEM-TACEs were performed per patient. A total of 197 events were reported including 2.6 % grade 4 and 1.5% grade 5, mostly related to post-embolization syndrome. Complete response, partial response and stable disease were 60.2%, 27.1% and 7.4% respectively providing an objective response and disease control rates of 87,3% and 94,7% respectively. 10% of patients were transplanted or resected. Median OS, PFS and TTUP is indicated in the table below. OS was 89.2%, 80.2% and 69.7% at 12, 18 and 24 months respectively. Conclusions: The treatment of patients with unresectable HCC with anthracycline loaded LifePearl showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS, TTUP and OS. [Table: see text]

A Retrospective Single Center Comparison of Cyclophosphamide Plus G-CSF Versus G-CSF Alone for Peripheral Blood Stem Cell (PBSC) Mobilisation Following First Line Therapy in Patients with Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1898-1898
Author(s):  
Richard S Whitmill ◽  
David J Lewis ◽  
David John Sutton ◽  
Jahanzeb Khawaja ◽  
Georgina Mayer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Lymphocyte Count ◽  
Progression Free Survival ◽  
Absolute Lymphocyte Count ◽  
Initial Therapy ◽  
Single Center ◽  
Free Survival ◽  
Neutropenic Sepsis ◽  
Cd34 Cells

Abstract Introduction Autologous transplantation is considered standard therapy for young and fit myeloma patients after initial therapy. Cyclophosphamide+ G-CSF is considered standard therapy for collection even though there is evidence for minimal anti-myeloma effect of cyclophosphamide, some increased short term toxicity and potential concerns regarding long term toxicity. There have been a few retrospective comparisons and one randomized study comparing cyclophosphamide based and G-CSF alone based PBSC collection. To our best knowledge they have not reported any impact in progression free survival (PFS) or overall survival (OS). We have compared here our myeloma patient cohort to explore these important endpoints. Patients and methods 89 patients (55 male and 34 female) who underwent first autologous transplant for myeloma between 2003 and 2010 were analysed in our study. Mobilization was with G-CSF alone in 45 patients (median age 58 yrs, range 38-70 yrs.) and cyclophosphamide and G-CSF in 44 (median age 58 yrs, range 41-74 yrs.). Cyclophosphamide was used at 3g/m2 and in both cases G-CSF used was lenogastrim at 10mcg/kg. There were 7 patients with ISS stage 3 in the G-CSF only group as compared to 10 in the Cyclophosphamide group. Prior chemotherapy was cyclophosphamide, thalidomide and dexamethasone in majority of cases (n=55) with no difference across both groups. Data regarding high risk genetics and pre-transplant response was unavailable. We collected data progression free survival, overall survival, harvest dose and engraftment kinetics. Data was analyzed using SPSS and log rank test. Results The median dose of stem cells collected with G-CSF alone was 3.59×106 CD34 cells/kg (range 1.84-8.09) where as with cyclophosphamide and G-CSF it was 3.8×106 CD34 cells/kg (range 1.6-13). There was no difference in engraftment between the two groups with median neutrophil engraftment (Absolute neutrophil count>0.20×109/L) at day 14 and platelet engraftment (>50×109/L) at day 15 and 16 respectively. Progression free survival was significantly better in G-CSF alone cohort (46 months vs. 38 months, P=0.016) (fig. a) Overall survival was better in the GCSF only group as well (113 months vs. 75 months, P=0.029) (fig b). In the 17 high risk patients PFS was much better in the G-CSF group (60months vs. 22 months, P=0.02) (Fig c). There were 4 (9%) admissions in the cyclophosphamide group due to neutropenic sepsis as compared to none in the G-CSF group. Discussion Cyclophosphamide and G-CSF may be associated with slightly higher stem cell yields but this margin is becoming smaller and not significant in the era of liberal plerixafor usage. In addition some patients are hospitalized due to neutropenic sepsis with this regimen. Our data shows anti-myeloma effects of cyclophosphamide +G-CSF is not demonstrated. There are ongoing studies from the Finland group which show no difference in the number of CD34+ cells collected after initial therapy with lenalidomide. The only difference is the number of days required for apheresis. In addition to above our single center experience shows both PFS and OS benefit for G-CSF only PBSC mobilization. . This may partially be explained by the slight difference in ISS risk stages in our patients but on censoring for ISS stage 3 these results were more pronounced. This is the first time we have seen any report point out towards a PFS and OS difference between two widely used mobilization regimens. This needs testing in a large randomized multi-center study to see if there is a difference and if so is this due to a change in milieu of lymphocytes. We have previously reported that absolute lymphocyte count on day 15 post autograft was reflective of a higher lymphocyte count in the apheresis bag in case of G-CSF only mobilizations as compared to cyclophosphamide +G-CSF. The absolute lymphocyte count on day 30 was a predictor for better OS. Figure 1. Progression free Survival Figure 1. Progression free Survival Figure 2. Overall survival Figure 2. Overall survival Figure 3. progression free survival for ISS score 3 Figure 3. progression free survival for ISS score 3 Disclosures Sutton: bayer: Honoraria. Paneesha:Janssen: Consultancy. Nikolousis:Alexion: Honoraria. Kishore:Jazz pharma: Honoraria; Celgene: Honoraria.

scholarly journals Challenges in the Current Management of Hepatocellular Carcinoma

2021 ◽  
Vol 6 (04) ◽  
pp. 269-274
Author(s):  
Soumya Jogi ◽  
Radha Varanasi ◽  
Sravani S Bantu ◽  
Sudha Saduvala ◽  
Ashish Manne
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Staging System ◽  
Convincing Evidence ◽  
Locoregional Therapy ◽  
Vegf Inhibitors ◽  
Stereotactic Radiation

Management of hepatocellular carcinoma (HCC) is complicated. Barcelona Clinic Liver Cancer (BCLC) staging system is widely used in risk stratifying HCC. It is different from anatomic staging (TNM) used in other cancers and is based on the liver function (Child-Pugh Score) and performance status at diagnosis along with tumor characteristics like size/number of primary, vascular invasion, and distant metastasis. Guidelines proposed by various liver societies help the treating physician select first-line therapy, but there are many limitations to them. Lack of reliable biomarkers that give objective information to monitor the response other than alpha-fetoprotein or radiological response is hurting the management strategies. There are no ideal predictors for recurrence and residual microscopic disease, especially after locoregional therapy (LRT) like surgical resection, ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and stereotactic radiation therapy (SBRT). Also, there is no convincing evidence to use adjunct therapy along with LRT in localized HCC. There is a need to identify the subset of HCC that would benefit from peri-procedural therapy. Recommendations for treating advanced HCC with macrovascular invasion is not uniform across the guidelines. Some propose LRT (TACE and/or TARE) or recommend systemic therapy only like tyrosine-kinase inhibitors (TKI) or Immune-checkpoint inhibitors (ICI). A considerable portion of patients have poor liver function (Child-Pugh Score C) at diagnosis. In this era of medicine, we should give them options other than supportive care, but unfortunately, it is the preferred option. This population needs special attention in trials. In current practice, there only 2-3 classes of drugs available like TKI, ICI, and vascular endothelial growth factor (VEGF) inhibitors. There is a need to explore more classes of liver-friendly drugs in treating HCC, and the enrolment of patients in clinical trials must be advised in the guidelines.

Real-Life Clinical Practice with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Center Experience Second Analysis

2015 ◽  
Vol 33 (6) ◽  
pp. 728-734 ◽  
Author(s):  
Tadaaki Arizumi ◽  
Kazuomi Ueshima ◽  
Mina Iwanishi ◽  
Hirokazu Chishina ◽  
Masashi Kono ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Response ◽  
Objective Response ◽  
Real Life ◽  
Progression Free Survival ◽  
University Hospital ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Center ◽  
Grade 3

Objectives: Sorafenib has become a standard therapy for advanced hepatocellular carcinoma following the demonstration of significant increase in progression-free survival as well as overall survival (OS) in the 2-phase III trials. We examined efficacy and adverse events (AEs) in patients treated with sorafenib over a 6-year period since approval in Japan. Methods: Two hundred and forty-one patients treated with sorafenib at the Kinki University Hospital were retrospectively analyzed clinically for the factors related to survival periods, tumor response evaluated by the Response Evaluation Criteria In Cancer of the Liver (RECICL) and AEs. Results: OS was 14.3 months. According to the RECICL, the objective response and disease control rates were 18.6% (43 of 241) and 61.1% (137 of 241), respectively. AEs were seen in 77.3% (187 of 241), with Grade 3 or higher in 23.6% (57 of 241). The most frequent AE was hand-foot skin reaction in 109 patients (45.0%), and 28 patients (11.8%) showed Grade 3 or higher. Significant factors contributing to the OS were treatment duration (p = 0.0204), up-to-7 criteria (p = 0.0400), increase of Child-Pugh score (p = 0.0008) and tumor response determined by the RECICL (p = 0.0007). Conclusion: Based on the analysis, using many cases at a single center, we concluded that continuation of treatment with sorafenib for ≥90 days without decrease of liver function was critical if tumor response was determined as stable disease or higher.

Alpha-Fetoprotein Response After Locoregional Therapy for Hepatocellular Carcinoma: Oncologic Marker of Radiologic Response, Progression, and Survival

2009 ◽  
Vol 27 (34) ◽  
pp. 5734-5742 ◽  
Author(s):  
Ahsun Riaz ◽  
Robert K. Ryu ◽  
Laura M. Kulik ◽  
Mary F. Mulcahy ◽  
Robert J. Lewandowski ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Screening Tool ◽  
Tumor Response ◽  
Multivariate Analyses ◽  
Progression Free Survival ◽  
Alpha Fetoprotein ◽  
Locoregional Therapy ◽  
Time To Progression ◽  
Free Survival

Purpose Alpha-fetoprotein (AFP) is considered to be an indicator of tumor activity in hepatocellular carcinoma (HCC). We present a novel correlation of AFP response to radiologic response, time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) in patients treated with locoregional therapies. Patients and Methods Four hundred sixty-three patients with HCC were treated with chemoembolization or radioembolization at our institution. One hundred twenty-five patients with baseline AFP higher than 200 ng/mL were studied for this analysis. AFP response was defined as more than 50% decrease from baseline. One hundred nineteen patients with follow-up imaging were studied for the AFP imaging correlation analysis. AFP response was correlated to radiologic response, TTP, PFS, and OS. Multivariate analyses were performed. Results Eighty-one patients (65%) showed AFP response. AFP response was seen in 26 (55%) of 47 and 55 (70%) of 78 of patients treated with chemoembolization and radioembolization, respectively (P = .12). WHO response was seen in 41 (53%) of 77 and 10 (24%) of 42 of AFP responders and nonresponders, respectively (P = .002). The hazard ratio (HR) for TTP in AFP nonresponders compared with responders was 2.8 (95% CI, 1.5 to 5.1). The HR for PFS was 4.2 (95% CI, 2.4 to 7.2) in AFP nonresponders compared with responders. The HR for OS in AFP nonresponders compared with responders was 5.5 (95% CI, 3.1 to 9.9) and 2.7 (95% CI, 1.6 to 4.6) on univariate and multivariate analyses, respectively. Conclusion The data presented support the use of AFP response seen after locoregional therapy as an ancillary method of assessing tumor response and survival, as well as an early objective screening tool for progression by imaging.

scholarly journals Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2)

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Masatoshi Kudo ◽  
Richard S. Finn ◽  
Manabu Morimoto ◽  
Kun-Ming Rau ◽  
Masafumi Ikeda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Intermediate Stage ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Locoregional Therapy ◽  
Hazards Model ◽  
Bclc Staging

<b><i>Background:</i></b> Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. <b><i>Methods:</i></b> A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0–1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score. <b><i>Results:</i></b> Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546–1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23–0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59–0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages. <b><i>Conclusions:</i></b> Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.

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