Hepatocellular Carcinoma

Key clinical point: Hepatocellular carcinoma patients who achieved complete remission with postoperative treatment after reduction hepatectomy fared better than those who achieved remission without postoperative treatment.

Major finding:  The 5-year overall survival rate and mean survival time after reduction hepatectomy were 15.7% and 28.40 months for the entire study population. The 5-year overall survival and mean survival times were 37.5% and 56.55 months, respectively, for patients who achieved complete remission with postoperative treatment, compared to 6.3% and 14.84 months, respectively, for those who achieved complete remission without postoperative treatment (P = 0.0041).

Study details: The data come from a review of 30 adults with advanced hepatocellular carcinoma who underwent reduction hepatectomy at a single center between 2000 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Asahi Y et al. World J Gastrointest Surg. 2021 Oct 27. doi: 10.4240/wjgs.v13.i10.1245.

Key clinical point: Hepatocellular carcinoma patients who achieved complete remission with postoperative treatment after reduction hepatectomy fared better than those who achieved remission without postoperative treatment.

Major finding:  The 5-year overall survival rate and mean survival time after reduction hepatectomy were 15.7% and 28.40 months for the entire study population. The 5-year overall survival and mean survival times were 37.5% and 56.55 months, respectively, for patients who achieved complete remission with postoperative treatment, compared to 6.3% and 14.84 months, respectively, for those who achieved complete remission without postoperative treatment (P = 0.0041).

Study details: The data come from a review of 30 adults with advanced hepatocellular carcinoma who underwent reduction hepatectomy at a single center between 2000 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Asahi Y et al. World J Gastrointest Surg. 2021 Oct 27. doi: 10.4240/wjgs.v13.i10.1245.

Key clinical point: Hepatocellular carcinoma patients who achieved complete remission with postoperative treatment after reduction hepatectomy fared better than those who achieved remission without postoperative treatment.

Major finding:  The 5-year overall survival rate and mean survival time after reduction hepatectomy were 15.7% and 28.40 months for the entire study population. The 5-year overall survival and mean survival times were 37.5% and 56.55 months, respectively, for patients who achieved complete remission with postoperative treatment, compared to 6.3% and 14.84 months, respectively, for those who achieved complete remission without postoperative treatment (P = 0.0041).

Study details: The data come from a review of 30 adults with advanced hepatocellular carcinoma who underwent reduction hepatectomy at a single center between 2000 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Asahi Y et al. World J Gastrointest Surg. 2021 Oct 27. doi: 10.4240/wjgs.v13.i10.1245.

Key clinical point: A combination of atezolizumab plus bevacizumab (ATZ+BV) caused less fatigue in HCC patients as a first-line therapy than when given as a later line therapy, based on the IMbrave150 criteria.

Major finding:  Treatment interruption due to fatigue was significantly higher in Child-Pugh B patients who received later treatment compared to Child-Pugh A patients who received early treatment (P = 0.030). In a multivariate analysis, neutrophil lymphocyte ratios and B-IMbrave150 criteria were independent predictors of objective response to the combination therapy (hazard ratios 4.591 and 4.108, respectively).

Study details: The data come from 94 adults with unresectable HCC treated with ATZ+BV at multiple centers. Of these, 46 Child-Pugh A patients received treatment early (B-IMbrave150-in) and 48 Child-Pugh B patients received the combination as first-line or later line therapy (B-IMbrave150-out).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chuma M et al. Hepatol Res. 2021 Nov 10. doi: 10.1111/hepr.13732. 

Key clinical point: A combination of atezolizumab plus bevacizumab (ATZ+BV) caused less fatigue in HCC patients as a first-line therapy than when given as a later line therapy, based on the IMbrave150 criteria.

Major finding:  Treatment interruption due to fatigue was significantly higher in Child-Pugh B patients who received later treatment compared to Child-Pugh A patients who received early treatment (P = 0.030). In a multivariate analysis, neutrophil lymphocyte ratios and B-IMbrave150 criteria were independent predictors of objective response to the combination therapy (hazard ratios 4.591 and 4.108, respectively).

Study details: The data come from 94 adults with unresectable HCC treated with ATZ+BV at multiple centers. Of these, 46 Child-Pugh A patients received treatment early (B-IMbrave150-in) and 48 Child-Pugh B patients received the combination as first-line or later line therapy (B-IMbrave150-out).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chuma M et al. Hepatol Res. 2021 Nov 10. doi: 10.1111/hepr.13732. 

Key clinical point: A combination of atezolizumab plus bevacizumab (ATZ+BV) caused less fatigue in HCC patients as a first-line therapy than when given as a later line therapy, based on the IMbrave150 criteria.

Major finding:  Treatment interruption due to fatigue was significantly higher in Child-Pugh B patients who received later treatment compared to Child-Pugh A patients who received early treatment (P = 0.030). In a multivariate analysis, neutrophil lymphocyte ratios and B-IMbrave150 criteria were independent predictors of objective response to the combination therapy (hazard ratios 4.591 and 4.108, respectively).

Study details: The data come from 94 adults with unresectable HCC treated with ATZ+BV at multiple centers. Of these, 46 Child-Pugh A patients received treatment early (B-IMbrave150-in) and 48 Child-Pugh B patients received the combination as first-line or later line therapy (B-IMbrave150-out).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chuma M et al. Hepatol Res. 2021 Nov 10. doi: 10.1111/hepr.13732. 

Key clinical point: Complete response after initial treatment with TACE was significantly associated with improved survival in adults with newly diagnosed hepatocellular carcinoma.

Major finding:  After their first treatment with TACE, 22.3% of the patients achieved complete response, and these patients had a better overall survival rate over a median follow-up period of 26.6 months than those who did not achieve complete response (35.8 months vs 24.0 months, P < 0.001).

Study details: The data come from 699 adults with newly diagnosed hepatocellular carcinoma who were initially treated with transarterial chemoembolization (TACE) between 2010 and 2013.

Disclosures: The study was supported by the Chang Gung Medical Research Fund and the National Science Council, Taiwan. The researchers had no financial conflicts to disclose.

Source: Peng C-W et al. Am J Cancer Res. 2021 Oct 15. 11(10): 4956–4965. PMID: 34765303. PMCID: PMC8569367.

Key clinical point: Complete response after initial treatment with TACE was significantly associated with improved survival in adults with newly diagnosed hepatocellular carcinoma.

Major finding:  After their first treatment with TACE, 22.3% of the patients achieved complete response, and these patients had a better overall survival rate over a median follow-up period of 26.6 months than those who did not achieve complete response (35.8 months vs 24.0 months, P < 0.001).

Study details: The data come from 699 adults with newly diagnosed hepatocellular carcinoma who were initially treated with transarterial chemoembolization (TACE) between 2010 and 2013.

Disclosures: The study was supported by the Chang Gung Medical Research Fund and the National Science Council, Taiwan. The researchers had no financial conflicts to disclose.

Source: Peng C-W et al. Am J Cancer Res. 2021 Oct 15. 11(10): 4956–4965. PMID: 34765303. PMCID: PMC8569367.

Key clinical point: Complete response after initial treatment with TACE was significantly associated with improved survival in adults with newly diagnosed hepatocellular carcinoma.

Major finding:  After their first treatment with TACE, 22.3% of the patients achieved complete response, and these patients had a better overall survival rate over a median follow-up period of 26.6 months than those who did not achieve complete response (35.8 months vs 24.0 months, P < 0.001).

Study details: The data come from 699 adults with newly diagnosed hepatocellular carcinoma who were initially treated with transarterial chemoembolization (TACE) between 2010 and 2013.

Disclosures: The study was supported by the Chang Gung Medical Research Fund and the National Science Council, Taiwan. The researchers had no financial conflicts to disclose.

Source: Peng C-W et al. Am J Cancer Res. 2021 Oct 15. 11(10): 4956–4965. PMID: 34765303. PMCID: PMC8569367.

Key clinical point: Baseline neutrophil-to-lymphocyte ratio (NLR), and delta NLR were predictors of overall survival in HCC patients treated with stereotactic body radiation therapy; however, neither platelet-to-lymphocyte ratio (PLR) nor delta PLR were predictive of survival.

Major finding:  Elevations in NLR and delta-NLR (dNLR) prior to SBRT in hepatocellular carcinoma patients were significant predictors of worse overall survival (P <0.001 and P = 0.011, respectively). 

Study details: The data come from a retrospective study of 93 adult HCC patients treated with stereotactic body radiation therapy (SBRT), with a median follow-up of 10.7 months.

Disclosures: The study was supported by the Tri-Service General Hospital. The researchers had no financial conflicts to disclose.  

Source: Hsiang C-W et al. J Hepatocell Carcinoma. 2021 Oct 29. doi: 10.2147/JHC.S334933.

Key clinical point: Baseline neutrophil-to-lymphocyte ratio (NLR), and delta NLR were predictors of overall survival in HCC patients treated with stereotactic body radiation therapy; however, neither platelet-to-lymphocyte ratio (PLR) nor delta PLR were predictive of survival.

Major finding:  Elevations in NLR and delta-NLR (dNLR) prior to SBRT in hepatocellular carcinoma patients were significant predictors of worse overall survival (P <0.001 and P = 0.011, respectively). 

Study details: The data come from a retrospective study of 93 adult HCC patients treated with stereotactic body radiation therapy (SBRT), with a median follow-up of 10.7 months.

Disclosures: The study was supported by the Tri-Service General Hospital. The researchers had no financial conflicts to disclose.  

Source: Hsiang C-W et al. J Hepatocell Carcinoma. 2021 Oct 29. doi: 10.2147/JHC.S334933.

Key clinical point: Baseline neutrophil-to-lymphocyte ratio (NLR), and delta NLR were predictors of overall survival in HCC patients treated with stereotactic body radiation therapy; however, neither platelet-to-lymphocyte ratio (PLR) nor delta PLR were predictive of survival.

Major finding:  Elevations in NLR and delta-NLR (dNLR) prior to SBRT in hepatocellular carcinoma patients were significant predictors of worse overall survival (P <0.001 and P = 0.011, respectively). 

Study details: The data come from a retrospective study of 93 adult HCC patients treated with stereotactic body radiation therapy (SBRT), with a median follow-up of 10.7 months.

Disclosures: The study was supported by the Tri-Service General Hospital. The researchers had no financial conflicts to disclose.  

Source: Hsiang C-W et al. J Hepatocell Carcinoma. 2021 Oct 29. doi: 10.2147/JHC.S334933.

Key clinical point: Fever following radiofrequency ablation in hepatocellular carcinoma patients was independently associated with younger age, low serum albumin level, general anesthesia, tumor size, and tumor number.

Major finding:  The adjusted odds ratios for the independent predictors of fever in these patients were 0.96 for younger age, 0.49 for low serum albumin level, 2.06 for general anesthesia, 1.52 for tumor size, and 1.71 for tumor number. HCC patients who developed fevers after radiofrequency ablation also had significantly longer hospital stays than those without fevers (9.06 days vs 5.50 days).

Study details: The data come from a retrospective study of 272 adults with new or recurrent hepatocellular carcinoma who underwent ultrasonography-guided radiofrequency ablation (RFA) between April 2014 and February 2019.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chen P-Y et al. Cancers (Basel). 2021 Oct 22. doi: 10.3390/cancers13215303.

Key clinical point: Fever following radiofrequency ablation in hepatocellular carcinoma patients was independently associated with younger age, low serum albumin level, general anesthesia, tumor size, and tumor number.

Major finding:  The adjusted odds ratios for the independent predictors of fever in these patients were 0.96 for younger age, 0.49 for low serum albumin level, 2.06 for general anesthesia, 1.52 for tumor size, and 1.71 for tumor number. HCC patients who developed fevers after radiofrequency ablation also had significantly longer hospital stays than those without fevers (9.06 days vs 5.50 days).

Study details: The data come from a retrospective study of 272 adults with new or recurrent hepatocellular carcinoma who underwent ultrasonography-guided radiofrequency ablation (RFA) between April 2014 and February 2019.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chen P-Y et al. Cancers (Basel). 2021 Oct 22. doi: 10.3390/cancers13215303.

Key clinical point: Fever following radiofrequency ablation in hepatocellular carcinoma patients was independently associated with younger age, low serum albumin level, general anesthesia, tumor size, and tumor number.

Major finding:  The adjusted odds ratios for the independent predictors of fever in these patients were 0.96 for younger age, 0.49 for low serum albumin level, 2.06 for general anesthesia, 1.52 for tumor size, and 1.71 for tumor number. HCC patients who developed fevers after radiofrequency ablation also had significantly longer hospital stays than those without fevers (9.06 days vs 5.50 days).

Study details: The data come from a retrospective study of 272 adults with new or recurrent hepatocellular carcinoma who underwent ultrasonography-guided radiofrequency ablation (RFA) between April 2014 and February 2019.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chen P-Y et al. Cancers (Basel). 2021 Oct 22. doi: 10.3390/cancers13215303.

Key clinical point: A multi-dimensional “combined index” model using artificial intelligence and SHG/TPEF microscopy was a stronger predictor of HCC recurrence than alpha fetoprotein levels in HCC patients who underwent curative hepatectomy.

Major finding:  The sensitivity and specificity of the combined index model was 81.8% and 90.5%, respectively, compared to 68.2% and 47.6%, respectively, for alpha fetoprotein level as a predictor of recurrent HCC.

Study details: The data come from a study of 81 adults with hepatocellular carcinoma who underwent curative intent hepatectomy. Researchers used fibrotic features of resected tissue to create a recurrence prediction model.

Disclosures: The study was supported by the Taiwan Ministry of Health. The researchers had no financial conflicts to disclose.

Source: Liu I-T et al. Cancers (Basel). 2021 Oct 23. doi: 10.3390/cancers13215323.

Key clinical point: A multi-dimensional “combined index” model using artificial intelligence and SHG/TPEF microscopy was a stronger predictor of HCC recurrence than alpha fetoprotein levels in HCC patients who underwent curative hepatectomy.

Major finding:  The sensitivity and specificity of the combined index model was 81.8% and 90.5%, respectively, compared to 68.2% and 47.6%, respectively, for alpha fetoprotein level as a predictor of recurrent HCC.

Study details: The data come from a study of 81 adults with hepatocellular carcinoma who underwent curative intent hepatectomy. Researchers used fibrotic features of resected tissue to create a recurrence prediction model.

Disclosures: The study was supported by the Taiwan Ministry of Health. The researchers had no financial conflicts to disclose.

Source: Liu I-T et al. Cancers (Basel). 2021 Oct 23. doi: 10.3390/cancers13215323.

Key clinical point: A multi-dimensional “combined index” model using artificial intelligence and SHG/TPEF microscopy was a stronger predictor of HCC recurrence than alpha fetoprotein levels in HCC patients who underwent curative hepatectomy.

Major finding:  The sensitivity and specificity of the combined index model was 81.8% and 90.5%, respectively, compared to 68.2% and 47.6%, respectively, for alpha fetoprotein level as a predictor of recurrent HCC.

Study details: The data come from a study of 81 adults with hepatocellular carcinoma who underwent curative intent hepatectomy. Researchers used fibrotic features of resected tissue to create a recurrence prediction model.

Disclosures: The study was supported by the Taiwan Ministry of Health. The researchers had no financial conflicts to disclose.

Source: Liu I-T et al. Cancers (Basel). 2021 Oct 23. doi: 10.3390/cancers13215323.

Key clinical point: Liver decompensation is a common late complication in HCC patients treated with SIRT, although overall survival rates surpass those in patients treated with sorafenib.

Major finding:  Liver decompensation, based on a Child-Pugh (CP) score of B7 or higher, occurred in significantly more HCC patients treated with SIRT compared to those treated with sorafenib (62% vs 27%) in a case-matched analysis. However, the median overall survival was significantly longer in SIRT-treated patients compared with sorafenib patients (16 months vs 9 months).

Study details: The data come from 69 adults with advanced HCC who underwent selective internal radiation therapy (SIRT) and had not developed radioembolization-induced liver disease (REILD).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: van Doorn DJ et al. Cancers (Basel). 2021 Oct 29. doi: 10.3390/cancers13215427.

Key clinical point: Liver decompensation is a common late complication in HCC patients treated with SIRT, although overall survival rates surpass those in patients treated with sorafenib.

Major finding:  Liver decompensation, based on a Child-Pugh (CP) score of B7 or higher, occurred in significantly more HCC patients treated with SIRT compared to those treated with sorafenib (62% vs 27%) in a case-matched analysis. However, the median overall survival was significantly longer in SIRT-treated patients compared with sorafenib patients (16 months vs 9 months).

Study details: The data come from 69 adults with advanced HCC who underwent selective internal radiation therapy (SIRT) and had not developed radioembolization-induced liver disease (REILD).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: van Doorn DJ et al. Cancers (Basel). 2021 Oct 29. doi: 10.3390/cancers13215427.

Key clinical point: Liver decompensation is a common late complication in HCC patients treated with SIRT, although overall survival rates surpass those in patients treated with sorafenib.

Major finding:  Liver decompensation, based on a Child-Pugh (CP) score of B7 or higher, occurred in significantly more HCC patients treated with SIRT compared to those treated with sorafenib (62% vs 27%) in a case-matched analysis. However, the median overall survival was significantly longer in SIRT-treated patients compared with sorafenib patients (16 months vs 9 months).

Study details: The data come from 69 adults with advanced HCC who underwent selective internal radiation therapy (SIRT) and had not developed radioembolization-induced liver disease (REILD).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: van Doorn DJ et al. Cancers (Basel). 2021 Oct 29. doi: 10.3390/cancers13215427.

Key clinical point: Patients who underwent laparoscopic liver resection for HCC had fewer complications and similar long-term outcomes to those who had open resection procedures.

Major finding:  Patients in the laparoscopic group had significantly fewer complications of Clavien-Dindo grade III or higher compared to those in the open group (14% vs 29%, P = .01). Overall survival rates at 1, 3, and 5 years were similar between the laparoscopic group and the open group, 90.9%, 79.3%, 70.5% vs 91.3%, 88.5%, 83.1%, respectively, and cumulative recurrence rates were not significantly different between the groups.

Study details: The data come from a retrospective study of 149 adults who underwent either laparoscopic or open liver resection between January 2008 and December 2019. Primary outcomes of overall survival and cumulative incidence of recurrence were assessed after propensity score matching.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ivanics T et al. Surgery. 2021 Nov 3. doi: 10.1016/j.surg.2021.10.017.

Key clinical point: Patients who underwent laparoscopic liver resection for HCC had fewer complications and similar long-term outcomes to those who had open resection procedures.

Major finding:  Patients in the laparoscopic group had significantly fewer complications of Clavien-Dindo grade III or higher compared to those in the open group (14% vs 29%, P = .01). Overall survival rates at 1, 3, and 5 years were similar between the laparoscopic group and the open group, 90.9%, 79.3%, 70.5% vs 91.3%, 88.5%, 83.1%, respectively, and cumulative recurrence rates were not significantly different between the groups.

Study details: The data come from a retrospective study of 149 adults who underwent either laparoscopic or open liver resection between January 2008 and December 2019. Primary outcomes of overall survival and cumulative incidence of recurrence were assessed after propensity score matching.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ivanics T et al. Surgery. 2021 Nov 3. doi: 10.1016/j.surg.2021.10.017.

Key clinical point: Patients who underwent laparoscopic liver resection for HCC had fewer complications and similar long-term outcomes to those who had open resection procedures.

Major finding:  Patients in the laparoscopic group had significantly fewer complications of Clavien-Dindo grade III or higher compared to those in the open group (14% vs 29%, P = .01). Overall survival rates at 1, 3, and 5 years were similar between the laparoscopic group and the open group, 90.9%, 79.3%, 70.5% vs 91.3%, 88.5%, 83.1%, respectively, and cumulative recurrence rates were not significantly different between the groups.

Study details: The data come from a retrospective study of 149 adults who underwent either laparoscopic or open liver resection between January 2008 and December 2019. Primary outcomes of overall survival and cumulative incidence of recurrence were assessed after propensity score matching.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ivanics T et al. Surgery. 2021 Nov 3. doi: 10.1016/j.surg.2021.10.017.

Tyrosine kinase inhibitors are the mainstay of systemic HCC therapy, however treatment at FDA-approved doses frequently leads to unacceptable toxicities, leading to reductions in the prescribed dose. Tokunaga et al. investigated whether lenvatinib dose intensity affects outcomes of patients with unresectable HCC. This was a retrospective analysis of 100 patients who received lenvatinib in the first- or later-line settings. Fifty-one patients started lenvatinib at the standard dose and 49 patients at a reduced dose. Dose reduction was carried out in 29 patients during cycle 1, and 62 patients during all cycles, with the cumulative dose reduction rate in all cycles of 79.9%.  Upon analysis, the authors confirmed that tumor responses and stable disease on lenvatinib correlated favorably with overall survival (OS) and time to progression (TTP). In addition, they found that higher dose intensity correlated with a higher response rate, though most (56%) patients were unable to maintain the recommended dose intensity due to unacceptable adverse events. In the final analysis, dose modification was not negatively associated with OS, TTP, or disease control with lenvatinib. Therefore, it remains reasonable to adjust the dose of lenvatinib to minimize toxicity that would affect adversely patient quality of life. Disease control remains the best predictor of longer survival, though it does not seem that highest doses of lenvatinib are needed to achieve that benefit.

Cabozantinib is approved for previously treated patients with unresectable HCC based on the phase III CELESTIAL trial that enrolled patients with Child Pugh A liver disease who had received up to two previous systemic treatments, one of which was sorafenib. This study demonstrated a statistically significant improvement in overall- and disease-free survival. Kelley et al analyzed the outcomes based on the albumin-bilirubin (ALBI) grade, an objective measure of liver function, of patients in the CELESTIAL trial. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin. The median OS was 17.5 months in the cabozantinib arm versus 11.4 months in the placebo arm for the ALBI grade 1 subgroup, and 8.0 months in the cabozantinib arm versus 6.4 months in the placebo arm for the ALBI grade 2 subgroup. The authors concluded that cabozantinib benefits patients with unresectable HCC irrespective of their ALBI grade, though liver dysfunction remains a poor prognostic indicator in patients with HCC.

Finally, Liu et al analyzed 27 patients with HCC (8 with extrahepatic spread) who received a combination of chemotherapy via hepatic artery infusion, anti-PD-1 immunotherapy, and tyrosine kinase inhibitor. Combination chemotherapy and immunotherapy resulted in a median progression-free survival of 10.6 months with a median 12.9 months’ follow up; the objective response rate was 63.0% and the disease control rate was 92.6%. The authors concluded that this combination of therapies was effective and well-tolerated, with a confirmatory phase 3 study planned.

Tyrosine kinase inhibitors are the mainstay of systemic HCC therapy, however treatment at FDA-approved doses frequently leads to unacceptable toxicities, leading to reductions in the prescribed dose. Tokunaga et al. investigated whether lenvatinib dose intensity affects outcomes of patients with unresectable HCC. This was a retrospective analysis of 100 patients who received lenvatinib in the first- or later-line settings. Fifty-one patients started lenvatinib at the standard dose and 49 patients at a reduced dose. Dose reduction was carried out in 29 patients during cycle 1, and 62 patients during all cycles, with the cumulative dose reduction rate in all cycles of 79.9%.  Upon analysis, the authors confirmed that tumor responses and stable disease on lenvatinib correlated favorably with overall survival (OS) and time to progression (TTP). In addition, they found that higher dose intensity correlated with a higher response rate, though most (56%) patients were unable to maintain the recommended dose intensity due to unacceptable adverse events. In the final analysis, dose modification was not negatively associated with OS, TTP, or disease control with lenvatinib. Therefore, it remains reasonable to adjust the dose of lenvatinib to minimize toxicity that would affect adversely patient quality of life. Disease control remains the best predictor of longer survival, though it does not seem that highest doses of lenvatinib are needed to achieve that benefit.

Cabozantinib is approved for previously treated patients with unresectable HCC based on the phase III CELESTIAL trial that enrolled patients with Child Pugh A liver disease who had received up to two previous systemic treatments, one of which was sorafenib. This study demonstrated a statistically significant improvement in overall- and disease-free survival. Kelley et al analyzed the outcomes based on the albumin-bilirubin (ALBI) grade, an objective measure of liver function, of patients in the CELESTIAL trial. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin. The median OS was 17.5 months in the cabozantinib arm versus 11.4 months in the placebo arm for the ALBI grade 1 subgroup, and 8.0 months in the cabozantinib arm versus 6.4 months in the placebo arm for the ALBI grade 2 subgroup. The authors concluded that cabozantinib benefits patients with unresectable HCC irrespective of their ALBI grade, though liver dysfunction remains a poor prognostic indicator in patients with HCC.

Finally, Liu et al analyzed 27 patients with HCC (8 with extrahepatic spread) who received a combination of chemotherapy via hepatic artery infusion, anti-PD-1 immunotherapy, and tyrosine kinase inhibitor. Combination chemotherapy and immunotherapy resulted in a median progression-free survival of 10.6 months with a median 12.9 months’ follow up; the objective response rate was 63.0% and the disease control rate was 92.6%. The authors concluded that this combination of therapies was effective and well-tolerated, with a confirmatory phase 3 study planned.

Tyrosine kinase inhibitors are the mainstay of systemic HCC therapy, however treatment at FDA-approved doses frequently leads to unacceptable toxicities, leading to reductions in the prescribed dose. Tokunaga et al. investigated whether lenvatinib dose intensity affects outcomes of patients with unresectable HCC. This was a retrospective analysis of 100 patients who received lenvatinib in the first- or later-line settings. Fifty-one patients started lenvatinib at the standard dose and 49 patients at a reduced dose. Dose reduction was carried out in 29 patients during cycle 1, and 62 patients during all cycles, with the cumulative dose reduction rate in all cycles of 79.9%.  Upon analysis, the authors confirmed that tumor responses and stable disease on lenvatinib correlated favorably with overall survival (OS) and time to progression (TTP). In addition, they found that higher dose intensity correlated with a higher response rate, though most (56%) patients were unable to maintain the recommended dose intensity due to unacceptable adverse events. In the final analysis, dose modification was not negatively associated with OS, TTP, or disease control with lenvatinib. Therefore, it remains reasonable to adjust the dose of lenvatinib to minimize toxicity that would affect adversely patient quality of life. Disease control remains the best predictor of longer survival, though it does not seem that highest doses of lenvatinib are needed to achieve that benefit.

Cabozantinib is approved for previously treated patients with unresectable HCC based on the phase III CELESTIAL trial that enrolled patients with Child Pugh A liver disease who had received up to two previous systemic treatments, one of which was sorafenib. This study demonstrated a statistically significant improvement in overall- and disease-free survival. Kelley et al analyzed the outcomes based on the albumin-bilirubin (ALBI) grade, an objective measure of liver function, of patients in the CELESTIAL trial. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin. The median OS was 17.5 months in the cabozantinib arm versus 11.4 months in the placebo arm for the ALBI grade 1 subgroup, and 8.0 months in the cabozantinib arm versus 6.4 months in the placebo arm for the ALBI grade 2 subgroup. The authors concluded that cabozantinib benefits patients with unresectable HCC irrespective of their ALBI grade, though liver dysfunction remains a poor prognostic indicator in patients with HCC.

Finally, Liu et al analyzed 27 patients with HCC (8 with extrahepatic spread) who received a combination of chemotherapy via hepatic artery infusion, anti-PD-1 immunotherapy, and tyrosine kinase inhibitor. Combination chemotherapy and immunotherapy resulted in a median progression-free survival of 10.6 months with a median 12.9 months’ follow up; the objective response rate was 63.0% and the disease control rate was 92.6%. The authors concluded that this combination of therapies was effective and well-tolerated, with a confirmatory phase 3 study planned.

Key clinical point: The primary outcome of local recurrence-free survival was significantly longer for lesions showing complete retention than for those showing incomplete retention, but overall survival was no different based on lipidiol retention.  

Major finding: After propensity score matching of 121 pairs of lesions with complete/incomplete retention, the median local recurrence-free survival for lesions exhibiting complete retention was 1,279 days, compared to a median of 819 days in the incomplete retention group (P = 0.030).

Study details: The data come from 198 adult patients with a total of 280 HCC lesions who underwent transarterial lipiodol injection and thermal ablation at three centers between June 2014 and September 2020.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Tan J et al. Abdom Radiol. 2021 Oct 12. doi: 10.1007/s00261-021-03305-3.

Key clinical point: The primary outcome of local recurrence-free survival was significantly longer for lesions showing complete retention than for those showing incomplete retention, but overall survival was no different based on lipidiol retention.  

Major finding: After propensity score matching of 121 pairs of lesions with complete/incomplete retention, the median local recurrence-free survival for lesions exhibiting complete retention was 1,279 days, compared to a median of 819 days in the incomplete retention group (P = 0.030).

Study details: The data come from 198 adult patients with a total of 280 HCC lesions who underwent transarterial lipiodol injection and thermal ablation at three centers between June 2014 and September 2020.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Tan J et al. Abdom Radiol. 2021 Oct 12. doi: 10.1007/s00261-021-03305-3.

Key clinical point: The primary outcome of local recurrence-free survival was significantly longer for lesions showing complete retention than for those showing incomplete retention, but overall survival was no different based on lipidiol retention.  

Major finding: After propensity score matching of 121 pairs of lesions with complete/incomplete retention, the median local recurrence-free survival for lesions exhibiting complete retention was 1,279 days, compared to a median of 819 days in the incomplete retention group (P = 0.030).

Study details: The data come from 198 adult patients with a total of 280 HCC lesions who underwent transarterial lipiodol injection and thermal ablation at three centers between June 2014 and September 2020.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Tan J et al. Abdom Radiol. 2021 Oct 12. doi: 10.1007/s00261-021-03305-3.