Title: Clinical efficacy of TACE using coil or gelatin sponge combined with targeted therapy
in the treatment of giant hepatocellular carcinoma with arterioportal fistulas
Version: 0 Date: 03 Nov 2024
Reviewer's report:
This retrospective study aimed to assess the effectiveness of spring coils or gelatin sponges for
embolization of giant HCC with hepatic arterioportal shunt (APS) in targeted therapy.
Targeted therapy was  Sorafenib (400 mg twice/day) or lenvatinib (#60 kg, 12 mg; <60 kg, 8
mg/day) in combination with or without 200 mg anti-programmed death 1(PD-1) and antibiotics
3–5 days before TACE treatment. In case of tumor progression after the first-line treatment, the
second-line systemic agent was regorafenib (80 mg–160 mg regorafenib once/day within 1–3
weeks in every 4-week cycle) combined with or without PD-1 inhibitors. The study population
included 81 patients with a large HCC complicated with the APS who were split into 2 groups
based on block-APS embolic agents defined as coil group and gelatin sponge group. Both  groups
received lipiodol TACE, after APS was correspondingly blocked with coil or gelatin sponge
(41 patients in the coil group, who received 6±3 TACEs, and 40 in the gelatin sponge groups
receiving 5.925±2 TACEs). Sorafenib or lenvatinib was administered 3/5 days before TACE.
The study results showed that both groups showed improvement in the fistula one month after
the first TACE and the last TACE compared to before treatment. The improvement (defined as
improvement by two grades: significant or insignificant improvement groups) in the fistula in
the coil group significantly outperformed the gelatin sponge group. There was no significant
difference in median OS and PFS between the two groups, however, both groups showed early
progression of intrahepatic lesions. The authors concluded that based on targeted therapy, spring
coils or gelatin sponge embolization were used for giant HCC combined with APS, which
improved the fistula significantly.
The study has clinical interest, however some issues need to be addressed.
-Enrolled patients: in the inclusion criteria the authors reported "liver function C grade". They
should further describe whether they were referring to Child-Pugh liver function grade. In this
case, they should provide detail about Child-Pugh B class patients (if they were included) since
this latter liver function class patients are not always good candidate for transarterial treatments
due to higher risk of liver function deterioration. This point deserve a comment and should be
discussed.
-safety profile and adverse events of TACE: the authors should report any TACE-related
adverse event (if any). Importantly, prognostic scores to predict the radiological response and
impact of TACE on residual liver function should also be investigated and explored. In this
regard, one of the most common TACE-related adverse event is a transient post-procedure
hypertransaminasemia that is potentially related to objective radiological response as recently
demonstrated (J Pers Med. 2021;11:1041. doi: 10.3390/jpm11101041.).   This may represent a
simple test in clinical practice that predicts the chance of response (or not) allows planning the
one-month clinical/radiological management and to plan
repeated/sequential intra-arterial treatment strategy in a tailored therapeutic approach.
-Systemic treatments: the  authors should report why their patients were treated with sorafenib
or lenvatinib, while the other approved first-line treatment based on bevacizumab plus
atezolizumab was not adminestered. Moreover, the second-line was based on regorafenib that
is currently approved only as second-line agent for patients receiving first-line sorafenib. In this
regard, there are  real-world studies describing Experience with regorafenib in the treatment of
hepatocellular carcinoma in clinical practice were regorafenib has been administered after other
first-line TKI agents and after immune checkpoint inhibitors.
Title: Clinical efficacy of TACE using coil or gelatin sponge combined with targeted therapy
in the treatment of giant hepatocellular carcinoma with arterioportal fistulas
Version: 0 Date: 03 Nov 2024
Reviewer's report:
This retrospective study aimed to assess the effectiveness of spring coils or gelatin sponges for
embolization of giant HCC with hepatic arterioportal shunt (APS) in targeted therapy.
Targeted therapy was  Sorafenib (400 mg twice/day) or lenvatinib (#60 kg, 12 mg; <60 kg, 8
mg/day) in combination with or without 200 mg anti-programmed death 1(PD-1) and antibiotics
3–5 days before TACE treatment. In case of tumor progression after the first-line treatment, the
second-line systemic agent was regorafenib (80 mg–160 mg regorafenib once/day within 1–3
weeks in every 4-week cycle) combined with or without PD-1 inhibitors. The study population
included 81 patients with a large HCC complicated with the APS who were split into 2 groups
based on block-APS embolic agents defined as coil group and gelatin sponge group. Both  groups
received lipiodol TACE, after APS was correspondingly blocked with coil or gelatin sponge
(41 patients in the coil group, who received 6±3 TACEs, and 40 in the gelatin sponge groups
receiving 5.925±2 TACEs). Sorafenib or lenvatinib was administered 3/5 days before TACE.
The study results showed that both groups showed improvement in the fistula one month after
the first TACE and the last TACE compared to before treatment. The improvement (defined as
improvement by two grades: significant or insignificant improvement groups) in the fistula in
the coil group significantly outperformed the gelatin sponge group. There was no significant
difference in median OS and PFS between the two groups, however, both groups showed early
progression of intrahepatic lesions. The authors concluded that based on targeted therapy, spring
coils or gelatin sponge embolization were used for giant HCC combined with APS, which
improved the fistula significantly.
The study has clinical interest, however some issues need to be addressed.
-Enrolled patients: in the inclusion criteria the authors reported "liver function C grade". They
should further describe whether they were referring to Child-Pugh liver function grade. In this
case, they should provide detail about Child-Pugh B class patients (if they were included) since
this latter liver function class patients are not always good candidate for transarterial treatments
due to higher risk of liver function deterioration. This point deserve a comment and should be
discussed.
-safety profile and adverse events of TACE: the authors should report any TACE-related
adverse event (if any). Importantly, prognostic scores to predict the radiological response and
impact of TACE on residual liver function should also be investigated and explored. In this
regard, one of the most common TACE-related adverse event is a transient post-procedure
hypertransaminasemia that is potentially related to objective radiological response as recently
demonstrated (J Pers Med. 2021;11:1041. doi: 10.3390/jpm11101041.).   This may represent a
simple test in clinical practice that predicts the chance of response (or not) allows planning the
one-month clinical/radiological management and to plan
repeated/sequential intra-arterial treatment strategy in a tailored therapeutic approach.
-Systemic treatments: the  authors should report why their patients were treated with sorafenib
or lenvatinib, while the other approved first-line treatment based on bevacizumab plus
atezolizumab was not adminestered. Moreover, the second-line was based on regorafenib that
is currently approved only as second-line agent for patients receiving first-line sorafenib. In this
regard, there are  real-world studies describing Experience with regorafenib in the treatment of
hepatocellular carcinoma in clinical practice were regorafenib has been administered after other
first-line TKI agents and after immune checkpoint inhibitors.
Please review this paper.
user
Title: Clinical efficacy of TACE using coil or gelatin sponge combined with targeted therapy
in the treatment of giant hepatocellular carcinoma with arterioportal fistulas
Version: 0 Date: 03 Nov 2024
Reviewer's report:
This retrospective study aimed to assess the effectiveness of spring coils or gelatin sponges for
embolization of giant HCC with hepatic arterioportal shunt (APS) in targeted therapy.
Targeted therapy was  Sorafenib (400 mg twice/day) or lenvatinib (#60 kg, 12 mg; <60 kg, 8
mg/day) in combination with or without 200 mg anti-programmed death 1(PD-1) and antibiotics
3–5 days before TACE treatment. In case of tumor progression after the first-line treatment, the
second-line systemic agent was regorafenib (80 mg–160 mg regorafenib once/day within 1–3
weeks in every 4-week cycle) combined with or without PD-1 inhibitors. The study population
included 81 patients with a large HCC complicated with the APS who were split into 2 groups
based on block-APS embolic agents defined as coil group and gelatin sponge group. Both  groups
received lipiodol TACE, after APS was correspondingly blocked with coil or gelatin sponge
(41 patients in the coil group, who received 6±3 TACEs, and 40 in the gelatin sponge groups
receiving 5.925±2 TACEs). Sorafenib or lenvatinib was administered 3/5 days before TACE.
The study results showed that both groups showed improvement in the fistula one month after
the first TACE and the last TACE compared to before treatment. The improvement (defined as
improvement by two grades: significant or insignificant improvement groups) in the fistula in
the coil group significantly outperformed the gelatin sponge group. There was no significant
difference in median OS and PFS between the two groups, however, both groups showed early
progression of intrahepatic lesions. The authors concluded that based on targeted therapy, spring
coils or gelatin sponge embolization were used for giant HCC combined with APS, which
improved the fistula significantly.
The study has clinical interest, however some issues need to be addressed.
-Enrolled patients: in the inclusion criteria the authors reported "liver function C grade". They
should further describe whether they were referring to Child-Pugh liver function grade. In this
case, they should provide detail about Child-Pugh B class patients (if they were included) since
this latter liver function class patients are not always good candidate for transarterial treatments
due to higher risk of liver function deterioration. This point deserve a comment and should be
discussed.
-safety profile and adverse events of TACE: the authors should report any TACE-related
adverse event (if any). Importantly, prognostic scores to predict the radiological response and
impact of TACE on residual liver function should also be investigated and explored. In this
regard, one of the most common TACE-related adverse event is a transient post-procedure
hypertransaminasemia that is potentially related to objective radiological response as recently
demonstrated (J Pers Med. 2021;11:1041. doi: 10.3390/jpm11101041.).   This may represent a
simple test in clinical practice that predicts the chance of response (or not) allows planning the
one-month clinical/radiological management and to plan
repeated/sequential intra-arterial treatment strategy in a tailored therapeutic approach.
-Systemic treatments: the  authors should report why their patients were treated with sorafenib
or lenvatinib, while the other approved first-line treatment based on bevacizumab plus
atezolizumab was not adminestered. Moreover, the second-line was based on regorafenib that
is currently approved only as second-line agent for patients receiving first-line sorafenib. In this
regard, there are  real-world studies describing Experience with regorafenib in the treatment of
hepatocellular carcinoma in clinical practice were regorafenib has been administered after other
first-line TKI agents and after immune checkpoint inhibitors.
assistant