A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

Background: Accurate identification of frail older patients at hospital admission may help target interventions; however, the extent to which risk prediction tools such as the frailty index can be utilized in the acute setting remains unclear.

Study design: Single-center prospective cohort study, during April 2015–January 2017.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Accurate identification of frail older patients at hospital admission may help target interventions; however, the extent to which risk prediction tools such as the frailty index can be utilized in the acute setting remains unclear.

Study design: Single-center prospective cohort study, during April 2015–January 2017.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Accurate identification of frail older patients at hospital admission may help target interventions; however, the extent to which risk prediction tools such as the frailty index can be utilized in the acute setting remains unclear.

Study design: Single-center prospective cohort study, during April 2015–January 2017.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Key clinical point: Hepatocellular carcinoma patients with intermediate or advanced disease experienced significantly improved outcomes when treated with transarterial chemoembolization (TACE) plus sorafenib vs. TACE only.

Major finding: Patients treated with TACE plus sorafenib showed a significant increase in average progression-free survival and overall survival compared to those treated with TACE only (21 months vs. 12 months and 32 months vs. 21 months, respectively).

Study details: The data come from a retrospective review of 85 adults with intermediate or advanced HCC who were treated with transarterial chemoembolization (TACE) alone or with sorafenib.

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

Source: Zou X et al. Cancer Manag Res. 2021 May 18. doi: 10.2147/CMAR.S304591. 

Key clinical point: Hepatocellular carcinoma patients with intermediate or advanced disease experienced significantly improved outcomes when treated with transarterial chemoembolization (TACE) plus sorafenib vs. TACE only.

Major finding: Patients treated with TACE plus sorafenib showed a significant increase in average progression-free survival and overall survival compared to those treated with TACE only (21 months vs. 12 months and 32 months vs. 21 months, respectively).

Study details: The data come from a retrospective review of 85 adults with intermediate or advanced HCC who were treated with transarterial chemoembolization (TACE) alone or with sorafenib.

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

Source: Zou X et al. Cancer Manag Res. 2021 May 18. doi: 10.2147/CMAR.S304591. 

Key clinical point: Hepatocellular carcinoma patients with intermediate or advanced disease experienced significantly improved outcomes when treated with transarterial chemoembolization (TACE) plus sorafenib vs. TACE only.

Major finding: Patients treated with TACE plus sorafenib showed a significant increase in average progression-free survival and overall survival compared to those treated with TACE only (21 months vs. 12 months and 32 months vs. 21 months, respectively).

Study details: The data come from a retrospective review of 85 adults with intermediate or advanced HCC who were treated with transarterial chemoembolization (TACE) alone or with sorafenib.

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

Source: Zou X et al. Cancer Manag Res. 2021 May 18. doi: 10.2147/CMAR.S304591. 

Key clinical point: Preoperative model for end-stage liver disease (MELD) score, post hepatectomy liver failure score (PHLF), and HCC recurrence were independent predictors of survival for HCC patients with cirrhosis who underwent curative liver resection.

Major finding: The preoperative MELD score and grades A, B, or C of the post hepatectomy liver failure score (PHLF) were significant independent predictors for survival in HCC patients with cirrhosis who underwent curative liver resection, with hazard ratios of 1.37 (MELD), 2.33 (grade A), 3.15 (grade B), 373.41 (grade C). HCC recurrence also was a significant independent predictor of survival (HA 11.67).

Study details: The data come from a review of 120 adults with HCC with cirrhosis who underwent curative resection.

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

Source: Elshaarawy O et al. World J Gastrointest Oncol. 2021 May 15. doi: 10.4251/wjgo.v13.i5.424.

Key clinical point: Preoperative model for end-stage liver disease (MELD) score, post hepatectomy liver failure score (PHLF), and HCC recurrence were independent predictors of survival for HCC patients with cirrhosis who underwent curative liver resection.

Major finding: The preoperative MELD score and grades A, B, or C of the post hepatectomy liver failure score (PHLF) were significant independent predictors for survival in HCC patients with cirrhosis who underwent curative liver resection, with hazard ratios of 1.37 (MELD), 2.33 (grade A), 3.15 (grade B), 373.41 (grade C). HCC recurrence also was a significant independent predictor of survival (HA 11.67).

Study details: The data come from a review of 120 adults with HCC with cirrhosis who underwent curative resection.

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

Source: Elshaarawy O et al. World J Gastrointest Oncol. 2021 May 15. doi: 10.4251/wjgo.v13.i5.424.

Key clinical point: Preoperative model for end-stage liver disease (MELD) score, post hepatectomy liver failure score (PHLF), and HCC recurrence were independent predictors of survival for HCC patients with cirrhosis who underwent curative liver resection.

Major finding: The preoperative MELD score and grades A, B, or C of the post hepatectomy liver failure score (PHLF) were significant independent predictors for survival in HCC patients with cirrhosis who underwent curative liver resection, with hazard ratios of 1.37 (MELD), 2.33 (grade A), 3.15 (grade B), 373.41 (grade C). HCC recurrence also was a significant independent predictor of survival (HA 11.67).

Study details: The data come from a review of 120 adults with HCC with cirrhosis who underwent curative resection.

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

Source: Elshaarawy O et al. World J Gastrointest Oncol. 2021 May 15. doi: 10.4251/wjgo.v13.i5.424.

Key clinical point: Hepatocellular carcinoma patients with lung or bone metastasis have a significantly worse prognosis than patients without these metastases.  

Major finding: In a multivariate analysis, independent predictors of poor overall survival and cancer-specific survival in HCC patients included age 52 years and older, male sex, low degree of tumor differentiation, N1 stage, lack of primary surgery or chemoradiotherapy, tumor size greater than 6 cm, and multiple organ metastasis.

Study details: The data come from a retrospective review of 3,126 adults with distant metastasis of hepatocellular carcinoma from 2010 to 2015; patients were grouped based on metastatic sites.

Disclosures: The study was funded by the Natural Science Foundation of Jiangsu Province. The researchers had no financial conflicts to disclose.  

Source: Zhan H et al. Front Oncol. 2021 May 10. doi: 10.3389/fonc.2021.652768.

Key clinical point: Hepatocellular carcinoma patients with lung or bone metastasis have a significantly worse prognosis than patients without these metastases.  

Major finding: In a multivariate analysis, independent predictors of poor overall survival and cancer-specific survival in HCC patients included age 52 years and older, male sex, low degree of tumor differentiation, N1 stage, lack of primary surgery or chemoradiotherapy, tumor size greater than 6 cm, and multiple organ metastasis.

Study details: The data come from a retrospective review of 3,126 adults with distant metastasis of hepatocellular carcinoma from 2010 to 2015; patients were grouped based on metastatic sites.

Disclosures: The study was funded by the Natural Science Foundation of Jiangsu Province. The researchers had no financial conflicts to disclose.  

Source: Zhan H et al. Front Oncol. 2021 May 10. doi: 10.3389/fonc.2021.652768.

Key clinical point: Hepatocellular carcinoma patients with lung or bone metastasis have a significantly worse prognosis than patients without these metastases.  

Major finding: In a multivariate analysis, independent predictors of poor overall survival and cancer-specific survival in HCC patients included age 52 years and older, male sex, low degree of tumor differentiation, N1 stage, lack of primary surgery or chemoradiotherapy, tumor size greater than 6 cm, and multiple organ metastasis.

Study details: The data come from a retrospective review of 3,126 adults with distant metastasis of hepatocellular carcinoma from 2010 to 2015; patients were grouped based on metastatic sites.

Disclosures: The study was funded by the Natural Science Foundation of Jiangsu Province. The researchers had no financial conflicts to disclose.  

Source: Zhan H et al. Front Oncol. 2021 May 10. doi: 10.3389/fonc.2021.652768.

Key clinical point: Arterial input function and quality were similar for HCC patients who received either gadoxetate disodium or gadobenate dimeglumine during the first 3 minutes after contrast injection during DCE-MRI. 

Major finding: Measures of arterial input function quality, modelled, and model-free perfusion parameters were not significantly different for patients who received either gadoxetate disodium or gadobenate dimeglumine during the first 3 minutes after contrast injection during DCE-MRI; P values ranged from 0.054-0.932. However, patients in the gadoxetate disodium group showed significantly lower liver parenchymal flow and later liver enhancement (P < 0.001).

Study details: The data come from a prospective study of 66 adults with 83 hepatocellular carcinomas who underwent dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI).

Disclosures: The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.  

Source: Stocker D et al. Eur Radiol. 2021 May 27. doi: 10.1007/s00330-021-08068-5.

Key clinical point: Arterial input function and quality were similar for HCC patients who received either gadoxetate disodium or gadobenate dimeglumine during the first 3 minutes after contrast injection during DCE-MRI. 

Major finding: Measures of arterial input function quality, modelled, and model-free perfusion parameters were not significantly different for patients who received either gadoxetate disodium or gadobenate dimeglumine during the first 3 minutes after contrast injection during DCE-MRI; P values ranged from 0.054-0.932. However, patients in the gadoxetate disodium group showed significantly lower liver parenchymal flow and later liver enhancement (P < 0.001).

Study details: The data come from a prospective study of 66 adults with 83 hepatocellular carcinomas who underwent dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI).

Disclosures: The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.  

Source: Stocker D et al. Eur Radiol. 2021 May 27. doi: 10.1007/s00330-021-08068-5.

Key clinical point: Arterial input function and quality were similar for HCC patients who received either gadoxetate disodium or gadobenate dimeglumine during the first 3 minutes after contrast injection during DCE-MRI. 

Major finding: Measures of arterial input function quality, modelled, and model-free perfusion parameters were not significantly different for patients who received either gadoxetate disodium or gadobenate dimeglumine during the first 3 minutes after contrast injection during DCE-MRI; P values ranged from 0.054-0.932. However, patients in the gadoxetate disodium group showed significantly lower liver parenchymal flow and later liver enhancement (P < 0.001).

Study details: The data come from a prospective study of 66 adults with 83 hepatocellular carcinomas who underwent dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI).

Disclosures: The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.  

Source: Stocker D et al. Eur Radiol. 2021 May 27. doi: 10.1007/s00330-021-08068-5.

Key clinical point: No difference in overall survival occurred between HCC patients treated with Lipiodol

Major finding: The average overall tumor reduction was 21.45%; 19.95% in the Lipiodol-only group and 22.95% in the combination group (P = 0.653). However, patients in the combination group showed significant improvement in various degrees of tumor response compared to the Lipiodol-only group (P = 0.010).

Study details: The data come from a prospective, randomized trial of 44 men and 17 women, aged 44-85 years, with hepatocellular carcinoma who underwent transarterial chemoembolization (cTACE) using Lipiodol only or with additional use of degradable starch microspheres (DSM).

Disclosures: The study was supported by PharmaCept GmbH, Berlin, Germany. The researchers had no financial conflicts to disclose.  

Source: Vogl TJ et al. Hepatol Int. 2021 May 27. doi: 10.1007/s12072-021-10193-8.

Key clinical point: No difference in overall survival occurred between HCC patients treated with Lipiodol

Major finding: The average overall tumor reduction was 21.45%; 19.95% in the Lipiodol-only group and 22.95% in the combination group (P = 0.653). However, patients in the combination group showed significant improvement in various degrees of tumor response compared to the Lipiodol-only group (P = 0.010).

Study details: The data come from a prospective, randomized trial of 44 men and 17 women, aged 44-85 years, with hepatocellular carcinoma who underwent transarterial chemoembolization (cTACE) using Lipiodol only or with additional use of degradable starch microspheres (DSM).

Disclosures: The study was supported by PharmaCept GmbH, Berlin, Germany. The researchers had no financial conflicts to disclose.  

Source: Vogl TJ et al. Hepatol Int. 2021 May 27. doi: 10.1007/s12072-021-10193-8.

Key clinical point: No difference in overall survival occurred between HCC patients treated with Lipiodol

Major finding: The average overall tumor reduction was 21.45%; 19.95% in the Lipiodol-only group and 22.95% in the combination group (P = 0.653). However, patients in the combination group showed significant improvement in various degrees of tumor response compared to the Lipiodol-only group (P = 0.010).

Study details: The data come from a prospective, randomized trial of 44 men and 17 women, aged 44-85 years, with hepatocellular carcinoma who underwent transarterial chemoembolization (cTACE) using Lipiodol only or with additional use of degradable starch microspheres (DSM).

Disclosures: The study was supported by PharmaCept GmbH, Berlin, Germany. The researchers had no financial conflicts to disclose.  

Source: Vogl TJ et al. Hepatol Int. 2021 May 27. doi: 10.1007/s12072-021-10193-8.

Key clinical point: Specific predictors for postoperative 90-day mortality for hepatocellular carcinoma patients after hepatic resection include Child-Pugh score, intraoperative blood loss, post-hepatectomy liver failure (PHLF), and peak serum bilirubin.

Major finding: The overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. 

Study details: The data come from a retrospective study of 244 adults with HCC who underwent elective hepatic resection between January 1, 2007, and December 31, 2017. 

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

Source: Lei GY et al. Visc Med. 2020 Oct 27. doi: 10.1159/000510811.

Key clinical point: Specific predictors for postoperative 90-day mortality for hepatocellular carcinoma patients after hepatic resection include Child-Pugh score, intraoperative blood loss, post-hepatectomy liver failure (PHLF), and peak serum bilirubin.

Major finding: The overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. 

Study details: The data come from a retrospective study of 244 adults with HCC who underwent elective hepatic resection between January 1, 2007, and December 31, 2017. 

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

Source: Lei GY et al. Visc Med. 2020 Oct 27. doi: 10.1159/000510811.

Key clinical point: Specific predictors for postoperative 90-day mortality for hepatocellular carcinoma patients after hepatic resection include Child-Pugh score, intraoperative blood loss, post-hepatectomy liver failure (PHLF), and peak serum bilirubin.

Major finding: The overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. 

Study details: The data come from a retrospective study of 244 adults with HCC who underwent elective hepatic resection between January 1, 2007, and December 31, 2017. 

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

Source: Lei GY et al. Visc Med. 2020 Oct 27. doi: 10.1159/000510811.

Key clinical point: The DEPDC1B gene restrained growth of tumors associated with HCC progression both in vitro and in vivo.

Major finding: Knockdown of DEPDC1B inhibited the progression of HCC by inhibiting cell proliferation, migration, and colony formation, also by promoting cell apoptosis in vitro.

Study details: The data come from an in vitro and in vivo analysis of DEPDC1B using immunohistochemical staining to detect expression in tumor tissues and normal tissues, and a  xenograft model was used to show the functions of DEPC1B on tumor growth in vivo.

Disclosures: The study was supported by the National Natural Science Foundation of China (No. 81602100) and Natural Science Foundation of Shanghai. The researchers had no financial conflicts to disclose.  

Source: Dang X-W et al. Aging. 2021 May 25. doi: 10.18632/aging.203016.

Key clinical point: The DEPDC1B gene restrained growth of tumors associated with HCC progression both in vitro and in vivo.

Major finding: Knockdown of DEPDC1B inhibited the progression of HCC by inhibiting cell proliferation, migration, and colony formation, also by promoting cell apoptosis in vitro.

Study details: The data come from an in vitro and in vivo analysis of DEPDC1B using immunohistochemical staining to detect expression in tumor tissues and normal tissues, and a  xenograft model was used to show the functions of DEPC1B on tumor growth in vivo.

Disclosures: The study was supported by the National Natural Science Foundation of China (No. 81602100) and Natural Science Foundation of Shanghai. The researchers had no financial conflicts to disclose.  

Source: Dang X-W et al. Aging. 2021 May 25. doi: 10.18632/aging.203016.

Key clinical point: The DEPDC1B gene restrained growth of tumors associated with HCC progression both in vitro and in vivo.

Major finding: Knockdown of DEPDC1B inhibited the progression of HCC by inhibiting cell proliferation, migration, and colony formation, also by promoting cell apoptosis in vitro.

Study details: The data come from an in vitro and in vivo analysis of DEPDC1B using immunohistochemical staining to detect expression in tumor tissues and normal tissues, and a  xenograft model was used to show the functions of DEPC1B on tumor growth in vivo.

Disclosures: The study was supported by the National Natural Science Foundation of China (No. 81602100) and Natural Science Foundation of Shanghai. The researchers had no financial conflicts to disclose.  

Source: Dang X-W et al. Aging. 2021 May 25. doi: 10.18632/aging.203016.