Discontinuing TNF inhibitors may not be required in PsA patients receiving BNT162b2 SARS-CoV-2 vaccine

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Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

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Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

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Clinical Edge Journal Scan Commentary: Prenatal Testing February 2022

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Dr. Longman scans the journals, so you don’t have to!

/*-->*/ Ryan Longman, MD
The field of obstetrics has always aimed to optimize the ability to screen pregnancies for aneuploidy; trisomy 21, trisomy 18, and trisomy 13. A recent study by Saito et al. in The Journal of Obstetric and Gynaecologic Research examined this issue. They did a retrospective analysis to evaluate the utility of adding a first trimester ultrasound screen to women that received positive NIPT results. The first trimester ultrasound included not only an evaluation for ultrasound markers of fetal aneuploidy but also a thorough anatomical assessment of the fetus for structural defects. They found that by adding the first trimester ultrasound, the positive predictive value (PPV) of NIPT for trisomy 18 increased (PPV for trisomy 13 and 21 were already 100% using NIPT alone). Although this finding is academically interesting and may aid in counseling patients with a positive result for trisomy 18 on NIPT, society recommendations are for diagnostic genetic testing with either chorionic villus sampling (CVS) or amniocentesis when abnormal results are found on NIPT, regardless of fetal ultrasound findings.

 

Prenatal ultrasound detects structural fetal abnormalities in about 3% of pregnancies. When structural fetal abnormalities are found on prenatal ultrasound, diagnostic genetic testing with either CVS or amniocentesis are recommended. Classically, this has meant fetal karyotype and chromosomal microarray testing (CMA). Recently, a new type of genetic testing has become available on fetal samples, whole-exome sequencing (WES). Smogavec et al. assesses this new technology and its ability to detect fetal genetic abnormalities. They retrospectively studied 90 fetuses with abnormalities detected on prenatal ultrasound that had normal CMA results and negative fluorescence in situ hybridization analysis testing for aneuploidy. They found WES testing added a 34.4% increased rate of detection of fetal genetic abnormalities. WES is a powerful tool for genetic diagnosis in fetuses with structural anomalies and should be considered anytime a karyotype or CMA is normal in a fetus with structural anomalies.

 

Lastly, prenatal genetic diagnosis at an early gestational age is critical for medical management of fetuses with anomalies. In a cohort study, Chen et al. assess the simultaneous combined use of CNV-seq and WES on testing turnaround time. They found by running the testing simultaneously, rather than sequentially, this would decrease testing time from over a month to less than 2 weeks. This strategy of testing could potentially decrease the time from detection of a fetal anomaly on ultrasound to a genetic diagnosis allowing for earlier counseling and medical guidance.

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Ryan Longman, MD, Associate Professor, Department of Obstetrics and Gynecology, University of Chicago, Pritzker School of Medicine; Director, Ultrasound and Genetics, Fetal Neonatal Care Center, University of Chicago Medical Center, Chicago, IL

Ryan Longman, MD, has disclosed no relevant financial relationships.

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Ryan Longman, MD, has disclosed no relevant financial relationships.

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Ryan Longman, MD, Associate Professor, Department of Obstetrics and Gynecology, University of Chicago, Pritzker School of Medicine; Director, Ultrasound and Genetics, Fetal Neonatal Care Center, University of Chicago Medical Center, Chicago, IL

Ryan Longman, MD, has disclosed no relevant financial relationships.

Dr. Longman scans the journals, so you don’t have to!
Dr. Longman scans the journals, so you don’t have to!

/*-->*/ Ryan Longman, MD
The field of obstetrics has always aimed to optimize the ability to screen pregnancies for aneuploidy; trisomy 21, trisomy 18, and trisomy 13. A recent study by Saito et al. in The Journal of Obstetric and Gynaecologic Research examined this issue. They did a retrospective analysis to evaluate the utility of adding a first trimester ultrasound screen to women that received positive NIPT results. The first trimester ultrasound included not only an evaluation for ultrasound markers of fetal aneuploidy but also a thorough anatomical assessment of the fetus for structural defects. They found that by adding the first trimester ultrasound, the positive predictive value (PPV) of NIPT for trisomy 18 increased (PPV for trisomy 13 and 21 were already 100% using NIPT alone). Although this finding is academically interesting and may aid in counseling patients with a positive result for trisomy 18 on NIPT, society recommendations are for diagnostic genetic testing with either chorionic villus sampling (CVS) or amniocentesis when abnormal results are found on NIPT, regardless of fetal ultrasound findings.

 

Prenatal ultrasound detects structural fetal abnormalities in about 3% of pregnancies. When structural fetal abnormalities are found on prenatal ultrasound, diagnostic genetic testing with either CVS or amniocentesis are recommended. Classically, this has meant fetal karyotype and chromosomal microarray testing (CMA). Recently, a new type of genetic testing has become available on fetal samples, whole-exome sequencing (WES). Smogavec et al. assesses this new technology and its ability to detect fetal genetic abnormalities. They retrospectively studied 90 fetuses with abnormalities detected on prenatal ultrasound that had normal CMA results and negative fluorescence in situ hybridization analysis testing for aneuploidy. They found WES testing added a 34.4% increased rate of detection of fetal genetic abnormalities. WES is a powerful tool for genetic diagnosis in fetuses with structural anomalies and should be considered anytime a karyotype or CMA is normal in a fetus with structural anomalies.

 

Lastly, prenatal genetic diagnosis at an early gestational age is critical for medical management of fetuses with anomalies. In a cohort study, Chen et al. assess the simultaneous combined use of CNV-seq and WES on testing turnaround time. They found by running the testing simultaneously, rather than sequentially, this would decrease testing time from over a month to less than 2 weeks. This strategy of testing could potentially decrease the time from detection of a fetal anomaly on ultrasound to a genetic diagnosis allowing for earlier counseling and medical guidance.

/*-->*/ Ryan Longman, MD
The field of obstetrics has always aimed to optimize the ability to screen pregnancies for aneuploidy; trisomy 21, trisomy 18, and trisomy 13. A recent study by Saito et al. in The Journal of Obstetric and Gynaecologic Research examined this issue. They did a retrospective analysis to evaluate the utility of adding a first trimester ultrasound screen to women that received positive NIPT results. The first trimester ultrasound included not only an evaluation for ultrasound markers of fetal aneuploidy but also a thorough anatomical assessment of the fetus for structural defects. They found that by adding the first trimester ultrasound, the positive predictive value (PPV) of NIPT for trisomy 18 increased (PPV for trisomy 13 and 21 were already 100% using NIPT alone). Although this finding is academically interesting and may aid in counseling patients with a positive result for trisomy 18 on NIPT, society recommendations are for diagnostic genetic testing with either chorionic villus sampling (CVS) or amniocentesis when abnormal results are found on NIPT, regardless of fetal ultrasound findings.

 

Prenatal ultrasound detects structural fetal abnormalities in about 3% of pregnancies. When structural fetal abnormalities are found on prenatal ultrasound, diagnostic genetic testing with either CVS or amniocentesis are recommended. Classically, this has meant fetal karyotype and chromosomal microarray testing (CMA). Recently, a new type of genetic testing has become available on fetal samples, whole-exome sequencing (WES). Smogavec et al. assesses this new technology and its ability to detect fetal genetic abnormalities. They retrospectively studied 90 fetuses with abnormalities detected on prenatal ultrasound that had normal CMA results and negative fluorescence in situ hybridization analysis testing for aneuploidy. They found WES testing added a 34.4% increased rate of detection of fetal genetic abnormalities. WES is a powerful tool for genetic diagnosis in fetuses with structural anomalies and should be considered anytime a karyotype or CMA is normal in a fetus with structural anomalies.

 

Lastly, prenatal genetic diagnosis at an early gestational age is critical for medical management of fetuses with anomalies. In a cohort study, Chen et al. assess the simultaneous combined use of CNV-seq and WES on testing turnaround time. They found by running the testing simultaneously, rather than sequentially, this would decrease testing time from over a month to less than 2 weeks. This strategy of testing could potentially decrease the time from detection of a fetal anomaly on ultrasound to a genetic diagnosis allowing for earlier counseling and medical guidance.

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Clinical Edge Journal Scan Commentary: HCC January 2022

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Dr. Damjanov scans the journals, so you don’t have to!

Nevena Damjanov, MD
Several novel options for the treatment of unresectable hepatocellular carcinoma (uHCC) have been evaluated over the past few years. This month, we will review recently published articles that address systemic therapies for uHCC.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

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Nevena Damjanov, MD, Professor, Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania; Chief, Department of Hematology-Oncology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania

Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

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Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

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Nevena Damjanov, MD, Professor, Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania; Chief, Department of Hematology-Oncology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania

Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

Dr. Damjanov scans the journals, so you don’t have to!
Dr. Damjanov scans the journals, so you don’t have to!

Nevena Damjanov, MD
Several novel options for the treatment of unresectable hepatocellular carcinoma (uHCC) have been evaluated over the past few years. This month, we will review recently published articles that address systemic therapies for uHCC.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

Nevena Damjanov, MD
Several novel options for the treatment of unresectable hepatocellular carcinoma (uHCC) have been evaluated over the past few years. This month, we will review recently published articles that address systemic therapies for uHCC.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

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mTORi-based immunosuppression prolongs post-liver transplant survival in HCC

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Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.

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Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.

Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.

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HCC: Percutaneous radiofrequency ablation outcomes not associated with NAFLD or MS

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Key clinical point: The presence of nonalcoholic fatty liver disease (NAFLD) or metabolic syndrome (MS) did not affect the long-term oncological outcomes in patients with hepatocellular carcinoma (HCC) treated with multibipolar percutaneous radiofrequency ablation (RFA).

Major finding: Neither NAFLD-HCC nor MS was associated with overall tumor recurrence (hazard ratio [HR], 1.12; P = .536 and HR, 0.99; P = .965, respectively) or overall survival (HR, 1.19; P = .45 and HR, 0.99; P = .980, respectively).

Study details: This multicenter retrospective study included 520 adult patients with HCC who underwent first-line multibipolar percutaneous RFA treatment.

Disclosures: The study did not receive any specific funding. T Dao, N Ganne-Carrié, and JC Nault reported receiving grants, speaker’s fees, personal fees, or invitations for medical meetings from various pharmaceutical companies.

Source: Nguyen N et al. Liver Int. 2021 Dec 11. doi: 10.1111/liv.15129.

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Key clinical point: The presence of nonalcoholic fatty liver disease (NAFLD) or metabolic syndrome (MS) did not affect the long-term oncological outcomes in patients with hepatocellular carcinoma (HCC) treated with multibipolar percutaneous radiofrequency ablation (RFA).

Major finding: Neither NAFLD-HCC nor MS was associated with overall tumor recurrence (hazard ratio [HR], 1.12; P = .536 and HR, 0.99; P = .965, respectively) or overall survival (HR, 1.19; P = .45 and HR, 0.99; P = .980, respectively).

Study details: This multicenter retrospective study included 520 adult patients with HCC who underwent first-line multibipolar percutaneous RFA treatment.

Disclosures: The study did not receive any specific funding. T Dao, N Ganne-Carrié, and JC Nault reported receiving grants, speaker’s fees, personal fees, or invitations for medical meetings from various pharmaceutical companies.

Source: Nguyen N et al. Liver Int. 2021 Dec 11. doi: 10.1111/liv.15129.

Key clinical point: The presence of nonalcoholic fatty liver disease (NAFLD) or metabolic syndrome (MS) did not affect the long-term oncological outcomes in patients with hepatocellular carcinoma (HCC) treated with multibipolar percutaneous radiofrequency ablation (RFA).

Major finding: Neither NAFLD-HCC nor MS was associated with overall tumor recurrence (hazard ratio [HR], 1.12; P = .536 and HR, 0.99; P = .965, respectively) or overall survival (HR, 1.19; P = .45 and HR, 0.99; P = .980, respectively).

Study details: This multicenter retrospective study included 520 adult patients with HCC who underwent first-line multibipolar percutaneous RFA treatment.

Disclosures: The study did not receive any specific funding. T Dao, N Ganne-Carrié, and JC Nault reported receiving grants, speaker’s fees, personal fees, or invitations for medical meetings from various pharmaceutical companies.

Source: Nguyen N et al. Liver Int. 2021 Dec 11. doi: 10.1111/liv.15129.

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Meta-analysis favors ICIs over standard care in unresectable HCC

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Key clinical point: Treatment with immune checkpoint inhibitors (ICIs) was associated with prolonged survival and better safety compared with standard care in patients with unresectable hepatocellular carcinoma (HCC).

Major finding: ICIs vs standard care were associated with superior overall survival (hazard ratio [HR], 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and overall response rate (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), including 1,657 patients with unresectable HCC treated with either ICIs (n=985) or standard care (n=672).

Disclosures: No source of funding was identified. The lead author and JPS Vasconcelos received grants and/or personal fees from various pharmaceutical companies.

Source: Jácome AA et al. JAMA Netw Open. 2021 Dec 6. doi: 10.1001/jamanetworkopen.2021.36128.

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Key clinical point: Treatment with immune checkpoint inhibitors (ICIs) was associated with prolonged survival and better safety compared with standard care in patients with unresectable hepatocellular carcinoma (HCC).

Major finding: ICIs vs standard care were associated with superior overall survival (hazard ratio [HR], 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and overall response rate (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), including 1,657 patients with unresectable HCC treated with either ICIs (n=985) or standard care (n=672).

Disclosures: No source of funding was identified. The lead author and JPS Vasconcelos received grants and/or personal fees from various pharmaceutical companies.

Source: Jácome AA et al. JAMA Netw Open. 2021 Dec 6. doi: 10.1001/jamanetworkopen.2021.36128.

Key clinical point: Treatment with immune checkpoint inhibitors (ICIs) was associated with prolonged survival and better safety compared with standard care in patients with unresectable hepatocellular carcinoma (HCC).

Major finding: ICIs vs standard care were associated with superior overall survival (hazard ratio [HR], 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and overall response rate (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), including 1,657 patients with unresectable HCC treated with either ICIs (n=985) or standard care (n=672).

Disclosures: No source of funding was identified. The lead author and JPS Vasconcelos received grants and/or personal fees from various pharmaceutical companies.

Source: Jácome AA et al. JAMA Netw Open. 2021 Dec 6. doi: 10.1001/jamanetworkopen.2021.36128.

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TARE may substitute surgical resection for initial treatment of large single nodular HCC

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Key clinical point: The better safety profile of transarterial radioembolization (TARE) together with comparable efficacy makes it a potential therapeutic alternative to surgical resection for large single nodular hepatocellular carcinoma (HCC).

Main finding: After inverse probability weighting, TARE vs surgical resection achieved similar overall survival (hazard ratio [HR], 0.98; P = .97), time to progression (HR, 1.10; P = .80), and time to intrahepatic progression (HR, 1.45; P = .30), along with a shorter hospital stay (3 days vs 12 days; P < .001) and lower patient proportion experiencing adverse events requiring intervention (0.0% vs 3.2%; P = .39).

Study details: Findings are from a retrospective cohort study including 557 adult patients with single nodular HCC measuring 5 cm who underwent either surgical resection (n=500) or TARE (n=57) shortly after diagnosis.

Disclosures: The authors reported no source of funding. Some of the authors received lecture fees or research grants from various sources.

Source: Kim J et al. J Nucl Med. 2021 Dec 9. doi: 10.2967/jnumed.121.263147.

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Key clinical point: The better safety profile of transarterial radioembolization (TARE) together with comparable efficacy makes it a potential therapeutic alternative to surgical resection for large single nodular hepatocellular carcinoma (HCC).

Main finding: After inverse probability weighting, TARE vs surgical resection achieved similar overall survival (hazard ratio [HR], 0.98; P = .97), time to progression (HR, 1.10; P = .80), and time to intrahepatic progression (HR, 1.45; P = .30), along with a shorter hospital stay (3 days vs 12 days; P < .001) and lower patient proportion experiencing adverse events requiring intervention (0.0% vs 3.2%; P = .39).

Study details: Findings are from a retrospective cohort study including 557 adult patients with single nodular HCC measuring 5 cm who underwent either surgical resection (n=500) or TARE (n=57) shortly after diagnosis.

Disclosures: The authors reported no source of funding. Some of the authors received lecture fees or research grants from various sources.

Source: Kim J et al. J Nucl Med. 2021 Dec 9. doi: 10.2967/jnumed.121.263147.

Key clinical point: The better safety profile of transarterial radioembolization (TARE) together with comparable efficacy makes it a potential therapeutic alternative to surgical resection for large single nodular hepatocellular carcinoma (HCC).

Main finding: After inverse probability weighting, TARE vs surgical resection achieved similar overall survival (hazard ratio [HR], 0.98; P = .97), time to progression (HR, 1.10; P = .80), and time to intrahepatic progression (HR, 1.45; P = .30), along with a shorter hospital stay (3 days vs 12 days; P < .001) and lower patient proportion experiencing adverse events requiring intervention (0.0% vs 3.2%; P = .39).

Study details: Findings are from a retrospective cohort study including 557 adult patients with single nodular HCC measuring 5 cm who underwent either surgical resection (n=500) or TARE (n=57) shortly after diagnosis.

Disclosures: The authors reported no source of funding. Some of the authors received lecture fees or research grants from various sources.

Source: Kim J et al. J Nucl Med. 2021 Dec 9. doi: 10.2967/jnumed.121.263147.

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Utilization of AFP to predict HCC recurrence after liver transplantation in waitlisted patients

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Key clinical point: Alpha-fetoprotein (AFP) levels during liver transplantation (LT) and their modulation while on the waitlist are predictors of hepatocellular carcinoma (HCC) recurrence after LT in patients meeting the Milan criteria.

Main finding: An AFP value >25.5 ng/mL (area under the receiver operating characteristic curve, 0.69) could strongly predict HCC recurrence after LT (subdistribution hazard ratio, 2.5; P = .01), which also showed a significant association with an increase in AFP levels by >20.8% while on the waitlist (P = .034).

Study details: The data are derived from a retrospective single-center study that analyzed 207 patients with HCC fulfilling the Milan criteria who were put on the waitlist for LT and had AFP levels >400 ng/mL at transplant.

Disclosures: Financial support for the study was provided by the association Friends of transplantation. The authors reported no conflict of interests.

Source: Magro B et al. Cancers. 2021 Nov 27. doi: 10.3390/cancers13235976.

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Key clinical point: Alpha-fetoprotein (AFP) levels during liver transplantation (LT) and their modulation while on the waitlist are predictors of hepatocellular carcinoma (HCC) recurrence after LT in patients meeting the Milan criteria.

Main finding: An AFP value >25.5 ng/mL (area under the receiver operating characteristic curve, 0.69) could strongly predict HCC recurrence after LT (subdistribution hazard ratio, 2.5; P = .01), which also showed a significant association with an increase in AFP levels by >20.8% while on the waitlist (P = .034).

Study details: The data are derived from a retrospective single-center study that analyzed 207 patients with HCC fulfilling the Milan criteria who were put on the waitlist for LT and had AFP levels >400 ng/mL at transplant.

Disclosures: Financial support for the study was provided by the association Friends of transplantation. The authors reported no conflict of interests.

Source: Magro B et al. Cancers. 2021 Nov 27. doi: 10.3390/cancers13235976.

Key clinical point: Alpha-fetoprotein (AFP) levels during liver transplantation (LT) and their modulation while on the waitlist are predictors of hepatocellular carcinoma (HCC) recurrence after LT in patients meeting the Milan criteria.

Main finding: An AFP value >25.5 ng/mL (area under the receiver operating characteristic curve, 0.69) could strongly predict HCC recurrence after LT (subdistribution hazard ratio, 2.5; P = .01), which also showed a significant association with an increase in AFP levels by >20.8% while on the waitlist (P = .034).

Study details: The data are derived from a retrospective single-center study that analyzed 207 patients with HCC fulfilling the Milan criteria who were put on the waitlist for LT and had AFP levels >400 ng/mL at transplant.

Disclosures: Financial support for the study was provided by the association Friends of transplantation. The authors reported no conflict of interests.

Source: Magro B et al. Cancers. 2021 Nov 27. doi: 10.3390/cancers13235976.

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Whole blood viscosity as a biomarker for distant metastasis and survival in HCC

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Key clinical point: High diastolic whole blood viscosity (WBV) may serve as a new independent factor associated with extrahepatic metastasis and poor survival in patients with hepatocellular carcinoma (HCC).

Main finding: After adjusting for confounding variables, high diastolic WBV was independently associated with extrahepatic metastasis (adjusted odds ratio, 23.41; P < .001) and poor survival (adjusted hazard ratio, 3.81; P < .001) and significantly predicted extrahepatic metastasis at an optimal cutoff of 16 cP (area under the receiver operating characteristic curve, 0.768; P < .001).

Study details: Findings are from a pilot retrospective study including 181 patients with HCC, of which 148 were treatment-naïve having preserved liver function and 33 received nivolumab.

Disclosures: The study was sponsored by Young Medical Scientist Research Grant through the Daewoong Foundation and the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea. The authors did not declare any conflict of interests.

Source: Han JW et al. PLoS ONE. 2021 Dec 2. doi: 10.1371/journal.pone.0260311.

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Key clinical point: High diastolic whole blood viscosity (WBV) may serve as a new independent factor associated with extrahepatic metastasis and poor survival in patients with hepatocellular carcinoma (HCC).

Main finding: After adjusting for confounding variables, high diastolic WBV was independently associated with extrahepatic metastasis (adjusted odds ratio, 23.41; P < .001) and poor survival (adjusted hazard ratio, 3.81; P < .001) and significantly predicted extrahepatic metastasis at an optimal cutoff of 16 cP (area under the receiver operating characteristic curve, 0.768; P < .001).

Study details: Findings are from a pilot retrospective study including 181 patients with HCC, of which 148 were treatment-naïve having preserved liver function and 33 received nivolumab.

Disclosures: The study was sponsored by Young Medical Scientist Research Grant through the Daewoong Foundation and the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea. The authors did not declare any conflict of interests.

Source: Han JW et al. PLoS ONE. 2021 Dec 2. doi: 10.1371/journal.pone.0260311.

Key clinical point: High diastolic whole blood viscosity (WBV) may serve as a new independent factor associated with extrahepatic metastasis and poor survival in patients with hepatocellular carcinoma (HCC).

Main finding: After adjusting for confounding variables, high diastolic WBV was independently associated with extrahepatic metastasis (adjusted odds ratio, 23.41; P < .001) and poor survival (adjusted hazard ratio, 3.81; P < .001) and significantly predicted extrahepatic metastasis at an optimal cutoff of 16 cP (area under the receiver operating characteristic curve, 0.768; P < .001).

Study details: Findings are from a pilot retrospective study including 181 patients with HCC, of which 148 were treatment-naïve having preserved liver function and 33 received nivolumab.

Disclosures: The study was sponsored by Young Medical Scientist Research Grant through the Daewoong Foundation and the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea. The authors did not declare any conflict of interests.

Source: Han JW et al. PLoS ONE. 2021 Dec 2. doi: 10.1371/journal.pone.0260311.

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Radiologic response to TACE-RT as a prognostic factor in advanced HCC with macroscopic vascular invasion

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Key clinical point: The modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined radiologic response rate of transarterial chemoembolization (TACE) plus radiotherapy (RT) among patients with advanced hepatocellular carcinoma (HCC) showing macroscopic vascular invasion (MVI) is an independent prognosticator for overall survival (OS).

Main finding: Responders vs nonresponders had significantly longer median OS at 2 months (23.1 months vs 8.0 months; adjusted hazard ratio [aHR], 3.194; P < .001) and 4 months (responders vs nonresponders: 26.5 months vs 9.3 months; aHR, 4.534; P < .001).

Study details: This was a retrospective review study including 427 patients with advanced HCC and MVI who received first-line treatment with TACE plus respiratory-gated 3-dimensional conformal RT in the 2-month analysis, whereas the patient number reduced to 355 in the 4-month analysis.

Disclosures: The study was supported by the Asan Institute for Life Sciences of Asan Medical Center, Seoul, Republic of Korea. The authors declared no conflict of interests.

Source: Jung J et al. Liver Cancer. 2021 Dec 7. doi: 10.1159/000521227.

 

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Key clinical point: The modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined radiologic response rate of transarterial chemoembolization (TACE) plus radiotherapy (RT) among patients with advanced hepatocellular carcinoma (HCC) showing macroscopic vascular invasion (MVI) is an independent prognosticator for overall survival (OS).

Main finding: Responders vs nonresponders had significantly longer median OS at 2 months (23.1 months vs 8.0 months; adjusted hazard ratio [aHR], 3.194; P < .001) and 4 months (responders vs nonresponders: 26.5 months vs 9.3 months; aHR, 4.534; P < .001).

Study details: This was a retrospective review study including 427 patients with advanced HCC and MVI who received first-line treatment with TACE plus respiratory-gated 3-dimensional conformal RT in the 2-month analysis, whereas the patient number reduced to 355 in the 4-month analysis.

Disclosures: The study was supported by the Asan Institute for Life Sciences of Asan Medical Center, Seoul, Republic of Korea. The authors declared no conflict of interests.

Source: Jung J et al. Liver Cancer. 2021 Dec 7. doi: 10.1159/000521227.

 

Key clinical point: The modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined radiologic response rate of transarterial chemoembolization (TACE) plus radiotherapy (RT) among patients with advanced hepatocellular carcinoma (HCC) showing macroscopic vascular invasion (MVI) is an independent prognosticator for overall survival (OS).

Main finding: Responders vs nonresponders had significantly longer median OS at 2 months (23.1 months vs 8.0 months; adjusted hazard ratio [aHR], 3.194; P < .001) and 4 months (responders vs nonresponders: 26.5 months vs 9.3 months; aHR, 4.534; P < .001).

Study details: This was a retrospective review study including 427 patients with advanced HCC and MVI who received first-line treatment with TACE plus respiratory-gated 3-dimensional conformal RT in the 2-month analysis, whereas the patient number reduced to 355 in the 4-month analysis.

Disclosures: The study was supported by the Asan Institute for Life Sciences of Asan Medical Center, Seoul, Republic of Korea. The authors declared no conflict of interests.

Source: Jung J et al. Liver Cancer. 2021 Dec 7. doi: 10.1159/000521227.

 

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