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Hemochromatosis variants may confer 10-fold higher risk of liver cancer
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
FROM JAMA
Vaccine regimen boosts immune response in malignant melanoma
“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.
The team described their study in Nature Cancer.
The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.
Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.
Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.
T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).
“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.
Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).
The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.
“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.
“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.
This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.
SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.
“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.
The team described their study in Nature Cancer.
The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.
Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.
Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.
T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).
“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.
Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).
The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.
“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.
“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.
This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.
SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.
“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.
The team described their study in Nature Cancer.
The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.
Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.
Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.
T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).
“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.
Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).
The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.
“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.
“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.
This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.
SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.
FROM NATURE CANCER
Genomic analysis reveals insights into pathogenesis of neuroblastoma
Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.
“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.
The group’s findings were published in Nature Communications.
The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.
The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).
MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).
“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.
Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.
Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.
“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.
Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.
“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.
SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.
Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.
“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.
The group’s findings were published in Nature Communications.
The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.
The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).
MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).
“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.
Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.
Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.
“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.
Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.
“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.
SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.
Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.
“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.
The group’s findings were published in Nature Communications.
The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.
The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).
MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).
“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.
Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.
Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.
“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.
Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.
“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.
SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.
FROM NATURE COMMUNICATIONS
'Cardio-obstetrics' tied to better outcome in pregnancy with CVD
A multidisciplinary cardio-obstetrics team-based care model may help improve cardiovascular care for pregnant women with cardiovascular disease (CVD), according to a recent study.
“We sought to describe clinical characteristics, maternal and fetal outcomes, and cardiovascular readmissions in a cohort of pregnant women with underlying CVD followed by a cardio-obstetrics team,” wrote Ella Magun, MD, of Columbia University, New York, and coauthors. Their report is in the Journal of the American College of Cardiology.
The researchers reported the outcomes of a retrospective cohort analysis involving 306 pregnant women with CVD, who were treated at a quaternary care hospital in New York City.
They defined cardio-obstetrics as a team-based collaborative approach to maternal care that includes maternal fetal medicine, cardiology, anesthesiology, neonatology, nursing, social work, and pharmacy.
More than half of the women in the cohort (53%) were Hispanic and Latino, and 74% were receiving Medicaid, suggesting low socioeconomic status. Key outcomes of interest were cardiovascular readmissions at 30 days, 90 days, and 1 year. Secondary endpoints included maternal death, need for a left ventricular assist device or heart transplantation, and fetal demise.
The most frequently observed forms of CVD were arrhythmias (29%), cardiomyopathy (24%), congenital heart disease (24%), valvular disease (16%), and coronary artery disease (4%). The median Cardiac Disease in Pregnancy (CARPREG II) score was 3, and 43% of women had a CARPREG II score of 4 or higher.
After a median follow-up of 2.6 years, the 30-day and 90-day cardiovascular readmission rates were 1.9% and 4.6%, which was lower than the national 30-day postpartum rate of readmission (3.6%). One maternal death (0.3%) occurred within a year of delivery (woman with Eisenmenger syndrome).
“Despite high CARPREG II scores in this patient population, we found low rates of maternal and fetal complications with a low rate of 30- and 90-day readmissions following delivery,” the researchers wrote.
Experts weigh in
“We’re seeing widely increasing interest in the implementation of cardio-obstetrics models for multidisciplinary collaborative care and initial studies suggest these team-based models improve pregnancy and postpartum outcomes for women with cardiac disease,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and professor at Baylor College of Medicine in Houston.
Dr. Magun and colleagues acknowledged that a key limitation of the present study was the retrospective, single-center design.
“With program expansions over the next 2-3 years, I expect to see an increasing number of prospective studies with larger sample sizes evaluating the impact of cardio-obstetrics teams on maternal morbidity and mortality,” Dr. Hollier said.
“These findings suggest that our cardio-obstetrics program may help provide improved cardiovascular care to an otherwise underserved population,” the authors concluded.
In an editorial accompanying the reports, Pamela Ouyang, MBBS, and Garima Sharma, MD, wrote that, although this study wasn’t designed to assess the benefit of cardio-obstetric teams relative to standard of care, its implementation of a multidisciplinary team-based care model showed excellent long-term outcomes.
The importance of coordinated postpartum follow-up with both cardiologists and obstetricians is becoming increasingly recognized, especially for women with poor pregnancy outcomes and with CVD that arises during pregnancy, such as pregnancy-associated spontaneous coronary artery dissection and peripartum cardiomyopathy, wrote Dr. Ouyang and Dr. Sharma, both with Johns Hopkins University in Baltimore.
“I’m very excited about the growing recognition of the importance of cardio-obstetrics and the emergence of many of these models of care at various institutions,” Melinda Davis, MD, of the University of Michigan in Ann Arbor, said in an interview.
“Over the next few years, I expect we will see several studies that show the benefits of the cardio-obstetrics model of care,” she explained. “Multicenter collaboration will be very important for learning about the optimal way to manage high-risk conditions during pregnancy.”
No funding sources were reported. The authors of this paper disclosed no conflicts of interest.
SOURCE: Magun E et al. JACC. 2020 Nov 3. doi: 10.1016/j.jacc.2020.08.071.
A multidisciplinary cardio-obstetrics team-based care model may help improve cardiovascular care for pregnant women with cardiovascular disease (CVD), according to a recent study.
“We sought to describe clinical characteristics, maternal and fetal outcomes, and cardiovascular readmissions in a cohort of pregnant women with underlying CVD followed by a cardio-obstetrics team,” wrote Ella Magun, MD, of Columbia University, New York, and coauthors. Their report is in the Journal of the American College of Cardiology.
The researchers reported the outcomes of a retrospective cohort analysis involving 306 pregnant women with CVD, who were treated at a quaternary care hospital in New York City.
They defined cardio-obstetrics as a team-based collaborative approach to maternal care that includes maternal fetal medicine, cardiology, anesthesiology, neonatology, nursing, social work, and pharmacy.
More than half of the women in the cohort (53%) were Hispanic and Latino, and 74% were receiving Medicaid, suggesting low socioeconomic status. Key outcomes of interest were cardiovascular readmissions at 30 days, 90 days, and 1 year. Secondary endpoints included maternal death, need for a left ventricular assist device or heart transplantation, and fetal demise.
The most frequently observed forms of CVD were arrhythmias (29%), cardiomyopathy (24%), congenital heart disease (24%), valvular disease (16%), and coronary artery disease (4%). The median Cardiac Disease in Pregnancy (CARPREG II) score was 3, and 43% of women had a CARPREG II score of 4 or higher.
After a median follow-up of 2.6 years, the 30-day and 90-day cardiovascular readmission rates were 1.9% and 4.6%, which was lower than the national 30-day postpartum rate of readmission (3.6%). One maternal death (0.3%) occurred within a year of delivery (woman with Eisenmenger syndrome).
“Despite high CARPREG II scores in this patient population, we found low rates of maternal and fetal complications with a low rate of 30- and 90-day readmissions following delivery,” the researchers wrote.
Experts weigh in
“We’re seeing widely increasing interest in the implementation of cardio-obstetrics models for multidisciplinary collaborative care and initial studies suggest these team-based models improve pregnancy and postpartum outcomes for women with cardiac disease,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and professor at Baylor College of Medicine in Houston.
Dr. Magun and colleagues acknowledged that a key limitation of the present study was the retrospective, single-center design.
“With program expansions over the next 2-3 years, I expect to see an increasing number of prospective studies with larger sample sizes evaluating the impact of cardio-obstetrics teams on maternal morbidity and mortality,” Dr. Hollier said.
“These findings suggest that our cardio-obstetrics program may help provide improved cardiovascular care to an otherwise underserved population,” the authors concluded.
In an editorial accompanying the reports, Pamela Ouyang, MBBS, and Garima Sharma, MD, wrote that, although this study wasn’t designed to assess the benefit of cardio-obstetric teams relative to standard of care, its implementation of a multidisciplinary team-based care model showed excellent long-term outcomes.
The importance of coordinated postpartum follow-up with both cardiologists and obstetricians is becoming increasingly recognized, especially for women with poor pregnancy outcomes and with CVD that arises during pregnancy, such as pregnancy-associated spontaneous coronary artery dissection and peripartum cardiomyopathy, wrote Dr. Ouyang and Dr. Sharma, both with Johns Hopkins University in Baltimore.
“I’m very excited about the growing recognition of the importance of cardio-obstetrics and the emergence of many of these models of care at various institutions,” Melinda Davis, MD, of the University of Michigan in Ann Arbor, said in an interview.
“Over the next few years, I expect we will see several studies that show the benefits of the cardio-obstetrics model of care,” she explained. “Multicenter collaboration will be very important for learning about the optimal way to manage high-risk conditions during pregnancy.”
No funding sources were reported. The authors of this paper disclosed no conflicts of interest.
SOURCE: Magun E et al. JACC. 2020 Nov 3. doi: 10.1016/j.jacc.2020.08.071.
A multidisciplinary cardio-obstetrics team-based care model may help improve cardiovascular care for pregnant women with cardiovascular disease (CVD), according to a recent study.
“We sought to describe clinical characteristics, maternal and fetal outcomes, and cardiovascular readmissions in a cohort of pregnant women with underlying CVD followed by a cardio-obstetrics team,” wrote Ella Magun, MD, of Columbia University, New York, and coauthors. Their report is in the Journal of the American College of Cardiology.
The researchers reported the outcomes of a retrospective cohort analysis involving 306 pregnant women with CVD, who were treated at a quaternary care hospital in New York City.
They defined cardio-obstetrics as a team-based collaborative approach to maternal care that includes maternal fetal medicine, cardiology, anesthesiology, neonatology, nursing, social work, and pharmacy.
More than half of the women in the cohort (53%) were Hispanic and Latino, and 74% were receiving Medicaid, suggesting low socioeconomic status. Key outcomes of interest were cardiovascular readmissions at 30 days, 90 days, and 1 year. Secondary endpoints included maternal death, need for a left ventricular assist device or heart transplantation, and fetal demise.
The most frequently observed forms of CVD were arrhythmias (29%), cardiomyopathy (24%), congenital heart disease (24%), valvular disease (16%), and coronary artery disease (4%). The median Cardiac Disease in Pregnancy (CARPREG II) score was 3, and 43% of women had a CARPREG II score of 4 or higher.
After a median follow-up of 2.6 years, the 30-day and 90-day cardiovascular readmission rates were 1.9% and 4.6%, which was lower than the national 30-day postpartum rate of readmission (3.6%). One maternal death (0.3%) occurred within a year of delivery (woman with Eisenmenger syndrome).
“Despite high CARPREG II scores in this patient population, we found low rates of maternal and fetal complications with a low rate of 30- and 90-day readmissions following delivery,” the researchers wrote.
Experts weigh in
“We’re seeing widely increasing interest in the implementation of cardio-obstetrics models for multidisciplinary collaborative care and initial studies suggest these team-based models improve pregnancy and postpartum outcomes for women with cardiac disease,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and professor at Baylor College of Medicine in Houston.
Dr. Magun and colleagues acknowledged that a key limitation of the present study was the retrospective, single-center design.
“With program expansions over the next 2-3 years, I expect to see an increasing number of prospective studies with larger sample sizes evaluating the impact of cardio-obstetrics teams on maternal morbidity and mortality,” Dr. Hollier said.
“These findings suggest that our cardio-obstetrics program may help provide improved cardiovascular care to an otherwise underserved population,” the authors concluded.
In an editorial accompanying the reports, Pamela Ouyang, MBBS, and Garima Sharma, MD, wrote that, although this study wasn’t designed to assess the benefit of cardio-obstetric teams relative to standard of care, its implementation of a multidisciplinary team-based care model showed excellent long-term outcomes.
The importance of coordinated postpartum follow-up with both cardiologists and obstetricians is becoming increasingly recognized, especially for women with poor pregnancy outcomes and with CVD that arises during pregnancy, such as pregnancy-associated spontaneous coronary artery dissection and peripartum cardiomyopathy, wrote Dr. Ouyang and Dr. Sharma, both with Johns Hopkins University in Baltimore.
“I’m very excited about the growing recognition of the importance of cardio-obstetrics and the emergence of many of these models of care at various institutions,” Melinda Davis, MD, of the University of Michigan in Ann Arbor, said in an interview.
“Over the next few years, I expect we will see several studies that show the benefits of the cardio-obstetrics model of care,” she explained. “Multicenter collaboration will be very important for learning about the optimal way to manage high-risk conditions during pregnancy.”
No funding sources were reported. The authors of this paper disclosed no conflicts of interest.
SOURCE: Magun E et al. JACC. 2020 Nov 3. doi: 10.1016/j.jacc.2020.08.071.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Novel assay may better detect urothelial carcinoma
The study authors developed a low-coverage whole-genome sequencing technique, called “Urine Exfoliated Cells Copy Number Aberration Detector” (UroCAD), to detect copy number variants in urine-exfoliated cells.
The team then tested whether UroCAD could detect urothelial carcinomas in a single-blinded trial.
Shuxiong Zeng, MD, PhD, of Naval Medical University, Shanghai, China, and colleagues described this work in Clinical Cancer Research.
Study details and results
The researchers first tested UroCAD on urine samples from a discovery cohort of 190 patients – 126 with urothelial carcinoma and 64 noncancer controls. In this group, UroCAD detected urothelial carcinoma with a sensitivity of 82.5% and a specificity of 96.9%.
The researchers also analyzed samples from a validation cohort of 95 patients – 56 with urothelial carcinoma and 39 noncancer controls.
In this cohort, UroCAD had significantly higher sensitivity than urine cytology (80.4% and 33.9%, respectively; P < .001) but similar specificity (94.9% and 100%, respectively; P = .49) for the detection of urothelial carcinoma.
Among seven patients with pTa tumors, UroCAD had a sensitivity of 71.4%, while urine cytology had a sensitivity of 0%.
UroCAD’s sensitivity was greater for high-grade than low-grade urothelial carcinomas (86.7% and 60.0%, respectively). The assay was also more sensitive for larger tumors, with sensitivities of 66.7% for tumors measuring 1 cm or less, 72% for tumors between 1 cm and 3 cm, and 95.5% for tumors larger than 3 cm.
“The relatively lower sensitivity of UroCAD for the detection of lower-grade or smaller tumors is not unexpected, as these tumors are less likely to have abundant chromosomal alterations,” study author Chuan-Liang Xu, MD, PhD, of the Changhai Hospital in Shanghai, explained in a press release. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination but not to replace it.”
The researchers noted that UroCAD positivity was associated with microscopic epithelial cells in cancer patients, and this suggests that insufficient exfoliative cells “might be the major technique limitation.”
Conclusions and next steps
“In summary, UroCAD could be a highly specific, robust, and noninvasive urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests,” the researchers concluded.
“Within the next 5 years, we can see UroCAD in a variety of commercial formats available to the global markets, including the USA,” Dr. Xu commented in an interview. “We see UroCAD as a disruptive technology in diagnosing and monitoring patients with urothelial carcinoma.
“In America, given the COVID-19 pandemic, we also envision UroCAD becoming commercially available in the form of a mailed, at-home collection kit for high-risk patients, which may also be purchased off the shelf at commercial pharmacies,” Dr. Xu added. “We hope UroCAD will make a positive clinical impact to the urology field.”
In a follow-up trial (NCT04432909), researchers are evaluating the utility of UroCAD in the surveillance of urothelial carcinoma.
The current research was supported by various funding sources in China. The authors reported having no conflicts of interest.
SOURCE: Zeng S et al. Clin Cancer Res. 2020 Oct 9. doi: 10.1158/1078-0432.CCR-20-0401.
The study authors developed a low-coverage whole-genome sequencing technique, called “Urine Exfoliated Cells Copy Number Aberration Detector” (UroCAD), to detect copy number variants in urine-exfoliated cells.
The team then tested whether UroCAD could detect urothelial carcinomas in a single-blinded trial.
Shuxiong Zeng, MD, PhD, of Naval Medical University, Shanghai, China, and colleagues described this work in Clinical Cancer Research.
Study details and results
The researchers first tested UroCAD on urine samples from a discovery cohort of 190 patients – 126 with urothelial carcinoma and 64 noncancer controls. In this group, UroCAD detected urothelial carcinoma with a sensitivity of 82.5% and a specificity of 96.9%.
The researchers also analyzed samples from a validation cohort of 95 patients – 56 with urothelial carcinoma and 39 noncancer controls.
In this cohort, UroCAD had significantly higher sensitivity than urine cytology (80.4% and 33.9%, respectively; P < .001) but similar specificity (94.9% and 100%, respectively; P = .49) for the detection of urothelial carcinoma.
Among seven patients with pTa tumors, UroCAD had a sensitivity of 71.4%, while urine cytology had a sensitivity of 0%.
UroCAD’s sensitivity was greater for high-grade than low-grade urothelial carcinomas (86.7% and 60.0%, respectively). The assay was also more sensitive for larger tumors, with sensitivities of 66.7% for tumors measuring 1 cm or less, 72% for tumors between 1 cm and 3 cm, and 95.5% for tumors larger than 3 cm.
“The relatively lower sensitivity of UroCAD for the detection of lower-grade or smaller tumors is not unexpected, as these tumors are less likely to have abundant chromosomal alterations,” study author Chuan-Liang Xu, MD, PhD, of the Changhai Hospital in Shanghai, explained in a press release. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination but not to replace it.”
The researchers noted that UroCAD positivity was associated with microscopic epithelial cells in cancer patients, and this suggests that insufficient exfoliative cells “might be the major technique limitation.”
Conclusions and next steps
“In summary, UroCAD could be a highly specific, robust, and noninvasive urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests,” the researchers concluded.
“Within the next 5 years, we can see UroCAD in a variety of commercial formats available to the global markets, including the USA,” Dr. Xu commented in an interview. “We see UroCAD as a disruptive technology in diagnosing and monitoring patients with urothelial carcinoma.
“In America, given the COVID-19 pandemic, we also envision UroCAD becoming commercially available in the form of a mailed, at-home collection kit for high-risk patients, which may also be purchased off the shelf at commercial pharmacies,” Dr. Xu added. “We hope UroCAD will make a positive clinical impact to the urology field.”
In a follow-up trial (NCT04432909), researchers are evaluating the utility of UroCAD in the surveillance of urothelial carcinoma.
The current research was supported by various funding sources in China. The authors reported having no conflicts of interest.
SOURCE: Zeng S et al. Clin Cancer Res. 2020 Oct 9. doi: 10.1158/1078-0432.CCR-20-0401.
The study authors developed a low-coverage whole-genome sequencing technique, called “Urine Exfoliated Cells Copy Number Aberration Detector” (UroCAD), to detect copy number variants in urine-exfoliated cells.
The team then tested whether UroCAD could detect urothelial carcinomas in a single-blinded trial.
Shuxiong Zeng, MD, PhD, of Naval Medical University, Shanghai, China, and colleagues described this work in Clinical Cancer Research.
Study details and results
The researchers first tested UroCAD on urine samples from a discovery cohort of 190 patients – 126 with urothelial carcinoma and 64 noncancer controls. In this group, UroCAD detected urothelial carcinoma with a sensitivity of 82.5% and a specificity of 96.9%.
The researchers also analyzed samples from a validation cohort of 95 patients – 56 with urothelial carcinoma and 39 noncancer controls.
In this cohort, UroCAD had significantly higher sensitivity than urine cytology (80.4% and 33.9%, respectively; P < .001) but similar specificity (94.9% and 100%, respectively; P = .49) for the detection of urothelial carcinoma.
Among seven patients with pTa tumors, UroCAD had a sensitivity of 71.4%, while urine cytology had a sensitivity of 0%.
UroCAD’s sensitivity was greater for high-grade than low-grade urothelial carcinomas (86.7% and 60.0%, respectively). The assay was also more sensitive for larger tumors, with sensitivities of 66.7% for tumors measuring 1 cm or less, 72% for tumors between 1 cm and 3 cm, and 95.5% for tumors larger than 3 cm.
“The relatively lower sensitivity of UroCAD for the detection of lower-grade or smaller tumors is not unexpected, as these tumors are less likely to have abundant chromosomal alterations,” study author Chuan-Liang Xu, MD, PhD, of the Changhai Hospital in Shanghai, explained in a press release. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination but not to replace it.”
The researchers noted that UroCAD positivity was associated with microscopic epithelial cells in cancer patients, and this suggests that insufficient exfoliative cells “might be the major technique limitation.”
Conclusions and next steps
“In summary, UroCAD could be a highly specific, robust, and noninvasive urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests,” the researchers concluded.
“Within the next 5 years, we can see UroCAD in a variety of commercial formats available to the global markets, including the USA,” Dr. Xu commented in an interview. “We see UroCAD as a disruptive technology in diagnosing and monitoring patients with urothelial carcinoma.
“In America, given the COVID-19 pandemic, we also envision UroCAD becoming commercially available in the form of a mailed, at-home collection kit for high-risk patients, which may also be purchased off the shelf at commercial pharmacies,” Dr. Xu added. “We hope UroCAD will make a positive clinical impact to the urology field.”
In a follow-up trial (NCT04432909), researchers are evaluating the utility of UroCAD in the surveillance of urothelial carcinoma.
The current research was supported by various funding sources in China. The authors reported having no conflicts of interest.
SOURCE: Zeng S et al. Clin Cancer Res. 2020 Oct 9. doi: 10.1158/1078-0432.CCR-20-0401.
FROM CLINICAL CANCER RESEARCH
New radiomic model may improve prognostication in meningioma
, according to a study published in the European Journal of Radiology.
The model – which combines conventional magnetic resonance imaging (cMRI), apparent diffusion coefficient (ADC) maps, and susceptibility weighted imaging (SWI) – was the best performer of all models tested.
Recent studies have shown that radiomic features from cMRI or ADC maps could build “a robust model to predict the grade of meningioma by using machine learning algorithms,” wrote study author Jianping Hu, MD, PhD, of Fujian Medical University in Fujian, China, and colleagues.
With that in mind, the researchers evaluated the role of radiomic models based on cMRI, ADC maps, and/or SWI in predicting meningioma grade.
Patients and models
The team retrospectively analyzed 514 patients with meningioma who underwent preoperative MRI assessment over a 10-year period. There were 316 patients included in the final analysis, 229 with low-grade (grade I) and 87 with high-grade (grade II-III) meningioma.
Radiomic features from cMRI, ADC maps, and SWI were extracted based on total tumor volume.
Using a nested leave-one-out cross-validation method, the researchers evaluated the prediction performance of various radiomic models, including cMRI, ADC, SWI, ADC plus SWI, cMRI plus ADC, cMRI plus SWI, and cMRI plus ADC plus SWI.
To establish the final prediction model, the researchers used least absolute shrinkage and selection operator feature selection and implemented a random forest classifier that was trained with and without subsampling. The area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction performance of each model.
Results
The model combining cMRI, ADC, and SWI had the best performance in predicting meningioma grade. The AUC of this model was 0.81 with subsampling and 0.84 without subsampling. The other models had an AUC range of 0.71-0.79 with subsampling and 0.75-0.80 without subsampling.
“Our results indicated that [the] multiparametric radiomic model based on cMRI, ADC map, and SWI [tended] to be the best model for the prediction of meningioma grade,” Dr. Hu and colleagues wrote.
Other recent studies have demonstrated that radiomic features from various imaging parameters, such as diffusion weighted imaging and cMRI, can establish robust prediction models for the prediction of meningioma grade, in which AUCs have ranged from 0.63 to 0.91.
While these findings are encouraging, the researchers acknowledged that these data should be interpreted with discretion as the cystic or necrotic areas of tumor were included in the analysis. In addition, the retrospective nature of the study could have introduced selection bias.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Hu J et al. Eur J Radiol. 2020 Aug 28. doi: 10.1016/j.ejrad.2020.109251.
, according to a study published in the European Journal of Radiology.
The model – which combines conventional magnetic resonance imaging (cMRI), apparent diffusion coefficient (ADC) maps, and susceptibility weighted imaging (SWI) – was the best performer of all models tested.
Recent studies have shown that radiomic features from cMRI or ADC maps could build “a robust model to predict the grade of meningioma by using machine learning algorithms,” wrote study author Jianping Hu, MD, PhD, of Fujian Medical University in Fujian, China, and colleagues.
With that in mind, the researchers evaluated the role of radiomic models based on cMRI, ADC maps, and/or SWI in predicting meningioma grade.
Patients and models
The team retrospectively analyzed 514 patients with meningioma who underwent preoperative MRI assessment over a 10-year period. There were 316 patients included in the final analysis, 229 with low-grade (grade I) and 87 with high-grade (grade II-III) meningioma.
Radiomic features from cMRI, ADC maps, and SWI were extracted based on total tumor volume.
Using a nested leave-one-out cross-validation method, the researchers evaluated the prediction performance of various radiomic models, including cMRI, ADC, SWI, ADC plus SWI, cMRI plus ADC, cMRI plus SWI, and cMRI plus ADC plus SWI.
To establish the final prediction model, the researchers used least absolute shrinkage and selection operator feature selection and implemented a random forest classifier that was trained with and without subsampling. The area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction performance of each model.
Results
The model combining cMRI, ADC, and SWI had the best performance in predicting meningioma grade. The AUC of this model was 0.81 with subsampling and 0.84 without subsampling. The other models had an AUC range of 0.71-0.79 with subsampling and 0.75-0.80 without subsampling.
“Our results indicated that [the] multiparametric radiomic model based on cMRI, ADC map, and SWI [tended] to be the best model for the prediction of meningioma grade,” Dr. Hu and colleagues wrote.
Other recent studies have demonstrated that radiomic features from various imaging parameters, such as diffusion weighted imaging and cMRI, can establish robust prediction models for the prediction of meningioma grade, in which AUCs have ranged from 0.63 to 0.91.
While these findings are encouraging, the researchers acknowledged that these data should be interpreted with discretion as the cystic or necrotic areas of tumor were included in the analysis. In addition, the retrospective nature of the study could have introduced selection bias.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Hu J et al. Eur J Radiol. 2020 Aug 28. doi: 10.1016/j.ejrad.2020.109251.
, according to a study published in the European Journal of Radiology.
The model – which combines conventional magnetic resonance imaging (cMRI), apparent diffusion coefficient (ADC) maps, and susceptibility weighted imaging (SWI) – was the best performer of all models tested.
Recent studies have shown that radiomic features from cMRI or ADC maps could build “a robust model to predict the grade of meningioma by using machine learning algorithms,” wrote study author Jianping Hu, MD, PhD, of Fujian Medical University in Fujian, China, and colleagues.
With that in mind, the researchers evaluated the role of radiomic models based on cMRI, ADC maps, and/or SWI in predicting meningioma grade.
Patients and models
The team retrospectively analyzed 514 patients with meningioma who underwent preoperative MRI assessment over a 10-year period. There were 316 patients included in the final analysis, 229 with low-grade (grade I) and 87 with high-grade (grade II-III) meningioma.
Radiomic features from cMRI, ADC maps, and SWI were extracted based on total tumor volume.
Using a nested leave-one-out cross-validation method, the researchers evaluated the prediction performance of various radiomic models, including cMRI, ADC, SWI, ADC plus SWI, cMRI plus ADC, cMRI plus SWI, and cMRI plus ADC plus SWI.
To establish the final prediction model, the researchers used least absolute shrinkage and selection operator feature selection and implemented a random forest classifier that was trained with and without subsampling. The area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction performance of each model.
Results
The model combining cMRI, ADC, and SWI had the best performance in predicting meningioma grade. The AUC of this model was 0.81 with subsampling and 0.84 without subsampling. The other models had an AUC range of 0.71-0.79 with subsampling and 0.75-0.80 without subsampling.
“Our results indicated that [the] multiparametric radiomic model based on cMRI, ADC map, and SWI [tended] to be the best model for the prediction of meningioma grade,” Dr. Hu and colleagues wrote.
Other recent studies have demonstrated that radiomic features from various imaging parameters, such as diffusion weighted imaging and cMRI, can establish robust prediction models for the prediction of meningioma grade, in which AUCs have ranged from 0.63 to 0.91.
While these findings are encouraging, the researchers acknowledged that these data should be interpreted with discretion as the cystic or necrotic areas of tumor were included in the analysis. In addition, the retrospective nature of the study could have introduced selection bias.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Hu J et al. Eur J Radiol. 2020 Aug 28. doi: 10.1016/j.ejrad.2020.109251.
FROM EUROPEAN JOURNAL OF RADIOLOGY
Study links gut microbiome and mRCC treatment outcomes
New research, published in European Urology, has revealed an association between gut microbial diversity and treatment outcomes for patients with metastatic renal cell carcinoma receiving checkpoint inhibitor therapy.
The findings suggest that metastatic renal cell carcinoma (mRCC) patients with a greater abundance of certain bacterial species derive clinical benefit from checkpoint inhibitor (CPI) treatment.
“We conducted a prospective observational study to determine the association between baseline gut microbial diversity and clinical benefit in patients with mRCC receiving CPIs,” study author Nicholas J. Salgia, an MD/PhD student at the State University of New York at Buffalo, and colleagues wrote.
The researchers collected stool samples from 31 mRCC patients within 7 days of them starting nivolumab monotherapy (77%) or nivolumab plus ipilimumab (23%). The microbial composition of each sample was evaluated using whole-metagenome sequencing at baseline, 1 month, and 3 months following treatment initiation.
In all, 58% of patients experienced a clinical benefit of treatment, which was defined as achieving a response or having stable disease for more than 4 months. There were 11 patients (35%) who achieved a complete or partial response and 7 (23%) who had stable disease for more than 4 months.
“Greater microbial diversity was associated with clinical benefit from CPI therapy (P = .001), and multiple species were associated with clinical benefit or lack thereof,” the researchers wrote.
In fact, there were 13 bacterial species with a linear discriminant analysis score of 3 or greater that distinguished between patients who had a clinical benefit (9 species) and those who did not (4 species).
The bacterial species with the greatest significance among patients with a clinical benefit were Bifidobacterium adolescentis (P = .002), Barnesiella intestinihominis (P = .002), Odoribacter splanchnicus (P = .006), and Bacteroides eggerthii (P = .009).
“These results suggest that certain species (e.g., [Prevotella] copri) appear to expand in relative abundance in patients deriving clinical benefit,” the researchers wrote.
The team also found that Akkermansia muciniphila increased in relative abundance in many patients experiencing clinical benefit and decreased in several patients not deriving clinical benefit.
“The patients with the highest benefit from cancer treatment were those with more microbial diversity but also those with a higher abundance of a specific bacterium known as Akkermansia muciniphila,” study author Sarah K. Highlander, PhD, of Translational Genomics Research Institute in Phoenix, said in a statement.
“This organism has been associated with benefit in other immunotherapy studies,” she explained.
The researchers acknowledged that a key limitation of this study was the method of stool collection. Given the use of a small, non–vacuum-sealed container, proliferation of aerobic bacteria could have occurred.
Based on the findings of this study, researchers are conducting a randomized clinical trial to evaluate the role of gut microbial modulation in CPI response. In this phase 1 study, researchers are investigating the use of frontline nivolumab plus ipilimumab, with or without CBM-588, a strain of Clostridium butyricum with both anti-inflammatory and immunomodulatory properties in the intestinal epithelium.
The current study was supported, in part, by a grant from Bristol-Myers Squibb. Several authors disclosed financial affiliations with multiple pharmaceutical companies.
SOURCE: Salgia NJ et al. Eur Urol. 2020 Aug 2. doi: 10.1016/j.eururo.2020.07.011.
New research, published in European Urology, has revealed an association between gut microbial diversity and treatment outcomes for patients with metastatic renal cell carcinoma receiving checkpoint inhibitor therapy.
The findings suggest that metastatic renal cell carcinoma (mRCC) patients with a greater abundance of certain bacterial species derive clinical benefit from checkpoint inhibitor (CPI) treatment.
“We conducted a prospective observational study to determine the association between baseline gut microbial diversity and clinical benefit in patients with mRCC receiving CPIs,” study author Nicholas J. Salgia, an MD/PhD student at the State University of New York at Buffalo, and colleagues wrote.
The researchers collected stool samples from 31 mRCC patients within 7 days of them starting nivolumab monotherapy (77%) or nivolumab plus ipilimumab (23%). The microbial composition of each sample was evaluated using whole-metagenome sequencing at baseline, 1 month, and 3 months following treatment initiation.
In all, 58% of patients experienced a clinical benefit of treatment, which was defined as achieving a response or having stable disease for more than 4 months. There were 11 patients (35%) who achieved a complete or partial response and 7 (23%) who had stable disease for more than 4 months.
“Greater microbial diversity was associated with clinical benefit from CPI therapy (P = .001), and multiple species were associated with clinical benefit or lack thereof,” the researchers wrote.
In fact, there were 13 bacterial species with a linear discriminant analysis score of 3 or greater that distinguished between patients who had a clinical benefit (9 species) and those who did not (4 species).
The bacterial species with the greatest significance among patients with a clinical benefit were Bifidobacterium adolescentis (P = .002), Barnesiella intestinihominis (P = .002), Odoribacter splanchnicus (P = .006), and Bacteroides eggerthii (P = .009).
“These results suggest that certain species (e.g., [Prevotella] copri) appear to expand in relative abundance in patients deriving clinical benefit,” the researchers wrote.
The team also found that Akkermansia muciniphila increased in relative abundance in many patients experiencing clinical benefit and decreased in several patients not deriving clinical benefit.
“The patients with the highest benefit from cancer treatment were those with more microbial diversity but also those with a higher abundance of a specific bacterium known as Akkermansia muciniphila,” study author Sarah K. Highlander, PhD, of Translational Genomics Research Institute in Phoenix, said in a statement.
“This organism has been associated with benefit in other immunotherapy studies,” she explained.
The researchers acknowledged that a key limitation of this study was the method of stool collection. Given the use of a small, non–vacuum-sealed container, proliferation of aerobic bacteria could have occurred.
Based on the findings of this study, researchers are conducting a randomized clinical trial to evaluate the role of gut microbial modulation in CPI response. In this phase 1 study, researchers are investigating the use of frontline nivolumab plus ipilimumab, with or without CBM-588, a strain of Clostridium butyricum with both anti-inflammatory and immunomodulatory properties in the intestinal epithelium.
The current study was supported, in part, by a grant from Bristol-Myers Squibb. Several authors disclosed financial affiliations with multiple pharmaceutical companies.
SOURCE: Salgia NJ et al. Eur Urol. 2020 Aug 2. doi: 10.1016/j.eururo.2020.07.011.
New research, published in European Urology, has revealed an association between gut microbial diversity and treatment outcomes for patients with metastatic renal cell carcinoma receiving checkpoint inhibitor therapy.
The findings suggest that metastatic renal cell carcinoma (mRCC) patients with a greater abundance of certain bacterial species derive clinical benefit from checkpoint inhibitor (CPI) treatment.
“We conducted a prospective observational study to determine the association between baseline gut microbial diversity and clinical benefit in patients with mRCC receiving CPIs,” study author Nicholas J. Salgia, an MD/PhD student at the State University of New York at Buffalo, and colleagues wrote.
The researchers collected stool samples from 31 mRCC patients within 7 days of them starting nivolumab monotherapy (77%) or nivolumab plus ipilimumab (23%). The microbial composition of each sample was evaluated using whole-metagenome sequencing at baseline, 1 month, and 3 months following treatment initiation.
In all, 58% of patients experienced a clinical benefit of treatment, which was defined as achieving a response or having stable disease for more than 4 months. There were 11 patients (35%) who achieved a complete or partial response and 7 (23%) who had stable disease for more than 4 months.
“Greater microbial diversity was associated with clinical benefit from CPI therapy (P = .001), and multiple species were associated with clinical benefit or lack thereof,” the researchers wrote.
In fact, there were 13 bacterial species with a linear discriminant analysis score of 3 or greater that distinguished between patients who had a clinical benefit (9 species) and those who did not (4 species).
The bacterial species with the greatest significance among patients with a clinical benefit were Bifidobacterium adolescentis (P = .002), Barnesiella intestinihominis (P = .002), Odoribacter splanchnicus (P = .006), and Bacteroides eggerthii (P = .009).
“These results suggest that certain species (e.g., [Prevotella] copri) appear to expand in relative abundance in patients deriving clinical benefit,” the researchers wrote.
The team also found that Akkermansia muciniphila increased in relative abundance in many patients experiencing clinical benefit and decreased in several patients not deriving clinical benefit.
“The patients with the highest benefit from cancer treatment were those with more microbial diversity but also those with a higher abundance of a specific bacterium known as Akkermansia muciniphila,” study author Sarah K. Highlander, PhD, of Translational Genomics Research Institute in Phoenix, said in a statement.
“This organism has been associated with benefit in other immunotherapy studies,” she explained.
The researchers acknowledged that a key limitation of this study was the method of stool collection. Given the use of a small, non–vacuum-sealed container, proliferation of aerobic bacteria could have occurred.
Based on the findings of this study, researchers are conducting a randomized clinical trial to evaluate the role of gut microbial modulation in CPI response. In this phase 1 study, researchers are investigating the use of frontline nivolumab plus ipilimumab, with or without CBM-588, a strain of Clostridium butyricum with both anti-inflammatory and immunomodulatory properties in the intestinal epithelium.
The current study was supported, in part, by a grant from Bristol-Myers Squibb. Several authors disclosed financial affiliations with multiple pharmaceutical companies.
SOURCE: Salgia NJ et al. Eur Urol. 2020 Aug 2. doi: 10.1016/j.eururo.2020.07.011.
FROM EUROPEAN UROLOGY
Experts publish imaging recommendations for pediatric COVID-19
A team of pulmonologists has synthesized the clinical and imaging characteristics of COVID-19 in children, and has devised recommendations for ordering imaging studies in suspected cases of the infection.
The review also included useful radiographic findings to help in the differential diagnosis of COVID-19 pneumonia from other respiratory infections. Alexandra M. Foust, DO, of Boston Children’s Hospital, and colleagues reported the summary of findings and recommendations in Pediatric Pulmonology.
“Pediatricians face numerous challenges created by increasing reports of severe COVID-19 related findings in affected children,” said Mary Cataletto, MD, of NYU Langone Health in Mineola, N.Y. “[The current review] represents a multinational collaboration to provide up to date information and key imaging findings to guide chest physicians caring for children with pneumonia symptoms during the COVID-19 pandemic.”
Clinical presentation in children
In general, pediatric patients infected with the virus show milder symptoms compared with adults, and based on the limited evidence reported to date, the most common clinical symptoms of COVID-19 in children are rhinorrhea and/or nasal congestion, fever and cough with sore throat, fatigue or dyspnea, and diarrhea.
As with other viral pneumonias in children, the laboratory parameters are usually nonspecific; however, while the complete blood count (CBC) is often normal, lymphopenia, thrombocytopenia, and neutropenia have been reported in some cases of pediatric COVID-19, the authors noted.
The current Centers for Disease Control and Prevention (CDC) recommendation for initial diagnosis of SARS-CoV-2 is obtaining a nasopharyngeal swab, followed by reverse transcription polymerase chain reaction (RT-PCR) testing, they explained.
Role of imaging in diagnosis
The researchers reported that current recommendations from the American College of Radiology (ACR) do not include chest computed tomography (CT) or chest radiography (CXR) as a upfront test to diagnose pediatric COVID-19, but they may still have a role in clinical monitoring, especially in patients with a moderate to severe disease course.
The potential benefits of utilizing radiologic evaluation, such as establishing a baseline for monitoring disease progression, must be balanced with potential drawbacks, which include radiation exposure, and reduced availability of imaging resources owing to necessary cleaning and air turnover time.
Recommendations for ordering imaging studies
Based on the most recent international guidelines for pediatric COVID-19 patient management, the authors developed an algorithm for performing imaging studies in suspected cases of COVID-19 pneumonia.
The purpose of the tool is to support clinical decision-making around the utilization of CXR and CT to evaluate pediatric COVID-19 pneumonia.
“The step by step algorithm addresses the selection, sequence and timing of imaging studies with multiple images illustrating key findings of COVID-19 pneumonia in the pediatric age group,” said Dr. Cataletto. “By synthesizing the available imaging case series and guidelines, this primer provides a useful tool for the practicing pulmonologist,” she explained.
Key recommendations: CXR
“For pediatric patients with suspected or known COVID-19 infection with moderate to severe clinical symptoms requiring hospitalization (i.e., hypoxia, moderate or severe dyspnea, signs of sepsis, shock, cardiovascular compromise, altered mentation), CXR is usually indicated to establish an imaging baseline and to assess for an alternative diagnosis,” they recommended.
“Sequential CXRs may be helpful to assess pediatric patients with COVID-19 who demonstrate worsening clinical symptoms or to assess response to supportive therapy,” they wrote.
Key recommendations: CT
“Due to the increased radiation sensitivity of pediatric patients, chest CT is not recommended as an initial diagnostic test for pediatric patients with known or suspected COVID-19 pneumonia,” they explained.
The guide also included several considerations around the differential diagnosis of COVID-19 pneumonia from other pediatric lung disorders, including immune-related conditions, infectious etiologies, hematological dyscrasias, and inhalation-related lung injury.
As best practice recommendations for COVID-19 continue to evolve, the availability of practical clinical decision-making tools becomes essential to ensure optimal patient care.
No funding sources or financial disclosures were reported in the manuscript.
SOURCE: Foust AM et al. Pediatr Pulmonol. 2020 May 28. doi: 10.1002/ppul.24870.
A team of pulmonologists has synthesized the clinical and imaging characteristics of COVID-19 in children, and has devised recommendations for ordering imaging studies in suspected cases of the infection.
The review also included useful radiographic findings to help in the differential diagnosis of COVID-19 pneumonia from other respiratory infections. Alexandra M. Foust, DO, of Boston Children’s Hospital, and colleagues reported the summary of findings and recommendations in Pediatric Pulmonology.
“Pediatricians face numerous challenges created by increasing reports of severe COVID-19 related findings in affected children,” said Mary Cataletto, MD, of NYU Langone Health in Mineola, N.Y. “[The current review] represents a multinational collaboration to provide up to date information and key imaging findings to guide chest physicians caring for children with pneumonia symptoms during the COVID-19 pandemic.”
Clinical presentation in children
In general, pediatric patients infected with the virus show milder symptoms compared with adults, and based on the limited evidence reported to date, the most common clinical symptoms of COVID-19 in children are rhinorrhea and/or nasal congestion, fever and cough with sore throat, fatigue or dyspnea, and diarrhea.
As with other viral pneumonias in children, the laboratory parameters are usually nonspecific; however, while the complete blood count (CBC) is often normal, lymphopenia, thrombocytopenia, and neutropenia have been reported in some cases of pediatric COVID-19, the authors noted.
The current Centers for Disease Control and Prevention (CDC) recommendation for initial diagnosis of SARS-CoV-2 is obtaining a nasopharyngeal swab, followed by reverse transcription polymerase chain reaction (RT-PCR) testing, they explained.
Role of imaging in diagnosis
The researchers reported that current recommendations from the American College of Radiology (ACR) do not include chest computed tomography (CT) or chest radiography (CXR) as a upfront test to diagnose pediatric COVID-19, but they may still have a role in clinical monitoring, especially in patients with a moderate to severe disease course.
The potential benefits of utilizing radiologic evaluation, such as establishing a baseline for monitoring disease progression, must be balanced with potential drawbacks, which include radiation exposure, and reduced availability of imaging resources owing to necessary cleaning and air turnover time.
Recommendations for ordering imaging studies
Based on the most recent international guidelines for pediatric COVID-19 patient management, the authors developed an algorithm for performing imaging studies in suspected cases of COVID-19 pneumonia.
The purpose of the tool is to support clinical decision-making around the utilization of CXR and CT to evaluate pediatric COVID-19 pneumonia.
“The step by step algorithm addresses the selection, sequence and timing of imaging studies with multiple images illustrating key findings of COVID-19 pneumonia in the pediatric age group,” said Dr. Cataletto. “By synthesizing the available imaging case series and guidelines, this primer provides a useful tool for the practicing pulmonologist,” she explained.
Key recommendations: CXR
“For pediatric patients with suspected or known COVID-19 infection with moderate to severe clinical symptoms requiring hospitalization (i.e., hypoxia, moderate or severe dyspnea, signs of sepsis, shock, cardiovascular compromise, altered mentation), CXR is usually indicated to establish an imaging baseline and to assess for an alternative diagnosis,” they recommended.
“Sequential CXRs may be helpful to assess pediatric patients with COVID-19 who demonstrate worsening clinical symptoms or to assess response to supportive therapy,” they wrote.
Key recommendations: CT
“Due to the increased radiation sensitivity of pediatric patients, chest CT is not recommended as an initial diagnostic test for pediatric patients with known or suspected COVID-19 pneumonia,” they explained.
The guide also included several considerations around the differential diagnosis of COVID-19 pneumonia from other pediatric lung disorders, including immune-related conditions, infectious etiologies, hematological dyscrasias, and inhalation-related lung injury.
As best practice recommendations for COVID-19 continue to evolve, the availability of practical clinical decision-making tools becomes essential to ensure optimal patient care.
No funding sources or financial disclosures were reported in the manuscript.
SOURCE: Foust AM et al. Pediatr Pulmonol. 2020 May 28. doi: 10.1002/ppul.24870.
A team of pulmonologists has synthesized the clinical and imaging characteristics of COVID-19 in children, and has devised recommendations for ordering imaging studies in suspected cases of the infection.
The review also included useful radiographic findings to help in the differential diagnosis of COVID-19 pneumonia from other respiratory infections. Alexandra M. Foust, DO, of Boston Children’s Hospital, and colleagues reported the summary of findings and recommendations in Pediatric Pulmonology.
“Pediatricians face numerous challenges created by increasing reports of severe COVID-19 related findings in affected children,” said Mary Cataletto, MD, of NYU Langone Health in Mineola, N.Y. “[The current review] represents a multinational collaboration to provide up to date information and key imaging findings to guide chest physicians caring for children with pneumonia symptoms during the COVID-19 pandemic.”
Clinical presentation in children
In general, pediatric patients infected with the virus show milder symptoms compared with adults, and based on the limited evidence reported to date, the most common clinical symptoms of COVID-19 in children are rhinorrhea and/or nasal congestion, fever and cough with sore throat, fatigue or dyspnea, and diarrhea.
As with other viral pneumonias in children, the laboratory parameters are usually nonspecific; however, while the complete blood count (CBC) is often normal, lymphopenia, thrombocytopenia, and neutropenia have been reported in some cases of pediatric COVID-19, the authors noted.
The current Centers for Disease Control and Prevention (CDC) recommendation for initial diagnosis of SARS-CoV-2 is obtaining a nasopharyngeal swab, followed by reverse transcription polymerase chain reaction (RT-PCR) testing, they explained.
Role of imaging in diagnosis
The researchers reported that current recommendations from the American College of Radiology (ACR) do not include chest computed tomography (CT) or chest radiography (CXR) as a upfront test to diagnose pediatric COVID-19, but they may still have a role in clinical monitoring, especially in patients with a moderate to severe disease course.
The potential benefits of utilizing radiologic evaluation, such as establishing a baseline for monitoring disease progression, must be balanced with potential drawbacks, which include radiation exposure, and reduced availability of imaging resources owing to necessary cleaning and air turnover time.
Recommendations for ordering imaging studies
Based on the most recent international guidelines for pediatric COVID-19 patient management, the authors developed an algorithm for performing imaging studies in suspected cases of COVID-19 pneumonia.
The purpose of the tool is to support clinical decision-making around the utilization of CXR and CT to evaluate pediatric COVID-19 pneumonia.
“The step by step algorithm addresses the selection, sequence and timing of imaging studies with multiple images illustrating key findings of COVID-19 pneumonia in the pediatric age group,” said Dr. Cataletto. “By synthesizing the available imaging case series and guidelines, this primer provides a useful tool for the practicing pulmonologist,” she explained.
Key recommendations: CXR
“For pediatric patients with suspected or known COVID-19 infection with moderate to severe clinical symptoms requiring hospitalization (i.e., hypoxia, moderate or severe dyspnea, signs of sepsis, shock, cardiovascular compromise, altered mentation), CXR is usually indicated to establish an imaging baseline and to assess for an alternative diagnosis,” they recommended.
“Sequential CXRs may be helpful to assess pediatric patients with COVID-19 who demonstrate worsening clinical symptoms or to assess response to supportive therapy,” they wrote.
Key recommendations: CT
“Due to the increased radiation sensitivity of pediatric patients, chest CT is not recommended as an initial diagnostic test for pediatric patients with known or suspected COVID-19 pneumonia,” they explained.
The guide also included several considerations around the differential diagnosis of COVID-19 pneumonia from other pediatric lung disorders, including immune-related conditions, infectious etiologies, hematological dyscrasias, and inhalation-related lung injury.
As best practice recommendations for COVID-19 continue to evolve, the availability of practical clinical decision-making tools becomes essential to ensure optimal patient care.
No funding sources or financial disclosures were reported in the manuscript.
SOURCE: Foust AM et al. Pediatr Pulmonol. 2020 May 28. doi: 10.1002/ppul.24870.
FROM PEDIATRIC PULMONOLOGY
Incidence of CNS tumors appears lower in Chinese children
, results of a population-based study suggest.
Adjusted incidence rates of CNS tumors were significantly higher among children from the U.S. Surveillance, Epidemiology, and End Results (SEER) database than among children from a cancer registry in Hong Kong.
Anthony P. Y. Liu, MBBS, MMedSc, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues reported these findings in JCO Global Oncology.
The Hong Kong cohort originally included 526 patients, but only 508 of them were included in the comparison with the SEER patients. The SEER cohorts included 447 patients of API descent and 5,047 patients of all ethnicities.
In all cohorts, patients were younger than 18 years of age and had been diagnosed with a primary CNS tumor during 1999-2016.
Results
Age-, sex-, and study period–adjusted incidence rates of CNS tumors were significantly higher in the SEER cohorts than in the Hong Kong cohort (P < .001). The adjusted incidence rates were:
- 2.51 per 100,000 children in the Hong Kong cohort.
- 3.26 per 100,000 children among APIs in the SEER cohort.
- 4.10 per 100,000 children among all ethnicities in the SEER cohort.
Incidence rates of most tumor types were significantly lower in the Hong Kong cohort than in the entire SEER cohort. This includes choroid plexus tumors (0.08 vs. 0.16; P = .045), ependymomas (0.18 vs. 0.31; P = .005), and glial and neuronal tumors (0.94 vs. 2.61; P < .001). However, incidence rates of germ cell tumors were significantly higher in the Hong Kong cohort (0.57 vs. 0.24; P < .001).
For the most part, there were no significant differences in incidence by histology between the Hong Kong cohort and the API SEER cohort. The exception was glial and neuronal tumors, for which the incidence rate was lower in the Hong Kong cohort than in the API SEER cohort (0.94 vs. 1.74; P < .001).
The 5-year overall survival rate was significantly lower in the Hong Kong cohort than in the API and entire SEER cohorts – 66.8% , 75.3%, and 78.7%, respectively (P < .001). This appears to be driven by inferior survival among Hong Kong patients with glial and neuronal tumors. For other tumor types, there were no significant differences in survival across the cohorts.
Interpretation
“Dr. Liu and colleagues have conducted a very nice epidemiological study, and their results suggest that the incidence of pediatric brain tumors is much lower in Hong Kong compared to the incidence in the United States,” noted Eric Bouffet, MD, of the University of Toronto.
“These results are intriguing, and it is clear that large epidemiological studies are needed to better understand the impact of ethnic, genetic, and socio-environmental factors linked to the incidence of childhood cancer, and in particular childhood brain tumors,” Dr. Bouffet added.
“My suspicion is that the lower incidence of brain tumors in Hong Kong may relate to the omission of patients who did not have a biopsy from the dataset,” said David Ziegler, MD, PhD, of the University of New South Wales in Kensington, Australia.
Dr. Liu and colleagues acknowledged that this study had limitations. The Hong Kong data do not represent the entire Chinese population, the SEER registry represents only 34.6% of the U.S. population, and the SEER registry has substandard ancestry designation for APIs. In addition, neither dataset included information on disease progression/recurrence or treatment details.
The study was supported by the American Lebanese Syrian Associated Charities and the Children’s Cancer Foundation, Hong Kong. Study authors disclosed relationships with MSD Oncology, Genentech, and Kazia Pharmaceutical.
Dr. Ziegler reported having no conflicts of interest. Dr. Bouffet disclosed relationships with Bristol-Myers Squibb and Roche.
SOURCE: Liu APY et al. JCO Glob Oncol. 2020 May 11. doi: 10.1200/JGO.19.00378.
, results of a population-based study suggest.
Adjusted incidence rates of CNS tumors were significantly higher among children from the U.S. Surveillance, Epidemiology, and End Results (SEER) database than among children from a cancer registry in Hong Kong.
Anthony P. Y. Liu, MBBS, MMedSc, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues reported these findings in JCO Global Oncology.
The Hong Kong cohort originally included 526 patients, but only 508 of them were included in the comparison with the SEER patients. The SEER cohorts included 447 patients of API descent and 5,047 patients of all ethnicities.
In all cohorts, patients were younger than 18 years of age and had been diagnosed with a primary CNS tumor during 1999-2016.
Results
Age-, sex-, and study period–adjusted incidence rates of CNS tumors were significantly higher in the SEER cohorts than in the Hong Kong cohort (P < .001). The adjusted incidence rates were:
- 2.51 per 100,000 children in the Hong Kong cohort.
- 3.26 per 100,000 children among APIs in the SEER cohort.
- 4.10 per 100,000 children among all ethnicities in the SEER cohort.
Incidence rates of most tumor types were significantly lower in the Hong Kong cohort than in the entire SEER cohort. This includes choroid plexus tumors (0.08 vs. 0.16; P = .045), ependymomas (0.18 vs. 0.31; P = .005), and glial and neuronal tumors (0.94 vs. 2.61; P < .001). However, incidence rates of germ cell tumors were significantly higher in the Hong Kong cohort (0.57 vs. 0.24; P < .001).
For the most part, there were no significant differences in incidence by histology between the Hong Kong cohort and the API SEER cohort. The exception was glial and neuronal tumors, for which the incidence rate was lower in the Hong Kong cohort than in the API SEER cohort (0.94 vs. 1.74; P < .001).
The 5-year overall survival rate was significantly lower in the Hong Kong cohort than in the API and entire SEER cohorts – 66.8% , 75.3%, and 78.7%, respectively (P < .001). This appears to be driven by inferior survival among Hong Kong patients with glial and neuronal tumors. For other tumor types, there were no significant differences in survival across the cohorts.
Interpretation
“Dr. Liu and colleagues have conducted a very nice epidemiological study, and their results suggest that the incidence of pediatric brain tumors is much lower in Hong Kong compared to the incidence in the United States,” noted Eric Bouffet, MD, of the University of Toronto.
“These results are intriguing, and it is clear that large epidemiological studies are needed to better understand the impact of ethnic, genetic, and socio-environmental factors linked to the incidence of childhood cancer, and in particular childhood brain tumors,” Dr. Bouffet added.
“My suspicion is that the lower incidence of brain tumors in Hong Kong may relate to the omission of patients who did not have a biopsy from the dataset,” said David Ziegler, MD, PhD, of the University of New South Wales in Kensington, Australia.
Dr. Liu and colleagues acknowledged that this study had limitations. The Hong Kong data do not represent the entire Chinese population, the SEER registry represents only 34.6% of the U.S. population, and the SEER registry has substandard ancestry designation for APIs. In addition, neither dataset included information on disease progression/recurrence or treatment details.
The study was supported by the American Lebanese Syrian Associated Charities and the Children’s Cancer Foundation, Hong Kong. Study authors disclosed relationships with MSD Oncology, Genentech, and Kazia Pharmaceutical.
Dr. Ziegler reported having no conflicts of interest. Dr. Bouffet disclosed relationships with Bristol-Myers Squibb and Roche.
SOURCE: Liu APY et al. JCO Glob Oncol. 2020 May 11. doi: 10.1200/JGO.19.00378.
, results of a population-based study suggest.
Adjusted incidence rates of CNS tumors were significantly higher among children from the U.S. Surveillance, Epidemiology, and End Results (SEER) database than among children from a cancer registry in Hong Kong.
Anthony P. Y. Liu, MBBS, MMedSc, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues reported these findings in JCO Global Oncology.
The Hong Kong cohort originally included 526 patients, but only 508 of them were included in the comparison with the SEER patients. The SEER cohorts included 447 patients of API descent and 5,047 patients of all ethnicities.
In all cohorts, patients were younger than 18 years of age and had been diagnosed with a primary CNS tumor during 1999-2016.
Results
Age-, sex-, and study period–adjusted incidence rates of CNS tumors were significantly higher in the SEER cohorts than in the Hong Kong cohort (P < .001). The adjusted incidence rates were:
- 2.51 per 100,000 children in the Hong Kong cohort.
- 3.26 per 100,000 children among APIs in the SEER cohort.
- 4.10 per 100,000 children among all ethnicities in the SEER cohort.
Incidence rates of most tumor types were significantly lower in the Hong Kong cohort than in the entire SEER cohort. This includes choroid plexus tumors (0.08 vs. 0.16; P = .045), ependymomas (0.18 vs. 0.31; P = .005), and glial and neuronal tumors (0.94 vs. 2.61; P < .001). However, incidence rates of germ cell tumors were significantly higher in the Hong Kong cohort (0.57 vs. 0.24; P < .001).
For the most part, there were no significant differences in incidence by histology between the Hong Kong cohort and the API SEER cohort. The exception was glial and neuronal tumors, for which the incidence rate was lower in the Hong Kong cohort than in the API SEER cohort (0.94 vs. 1.74; P < .001).
The 5-year overall survival rate was significantly lower in the Hong Kong cohort than in the API and entire SEER cohorts – 66.8% , 75.3%, and 78.7%, respectively (P < .001). This appears to be driven by inferior survival among Hong Kong patients with glial and neuronal tumors. For other tumor types, there were no significant differences in survival across the cohorts.
Interpretation
“Dr. Liu and colleagues have conducted a very nice epidemiological study, and their results suggest that the incidence of pediatric brain tumors is much lower in Hong Kong compared to the incidence in the United States,” noted Eric Bouffet, MD, of the University of Toronto.
“These results are intriguing, and it is clear that large epidemiological studies are needed to better understand the impact of ethnic, genetic, and socio-environmental factors linked to the incidence of childhood cancer, and in particular childhood brain tumors,” Dr. Bouffet added.
“My suspicion is that the lower incidence of brain tumors in Hong Kong may relate to the omission of patients who did not have a biopsy from the dataset,” said David Ziegler, MD, PhD, of the University of New South Wales in Kensington, Australia.
Dr. Liu and colleagues acknowledged that this study had limitations. The Hong Kong data do not represent the entire Chinese population, the SEER registry represents only 34.6% of the U.S. population, and the SEER registry has substandard ancestry designation for APIs. In addition, neither dataset included information on disease progression/recurrence or treatment details.
The study was supported by the American Lebanese Syrian Associated Charities and the Children’s Cancer Foundation, Hong Kong. Study authors disclosed relationships with MSD Oncology, Genentech, and Kazia Pharmaceutical.
Dr. Ziegler reported having no conflicts of interest. Dr. Bouffet disclosed relationships with Bristol-Myers Squibb and Roche.
SOURCE: Liu APY et al. JCO Glob Oncol. 2020 May 11. doi: 10.1200/JGO.19.00378.
FROM JCO GLOBAL ONCOLOGY
New diagnostic CT scan model predicts pulmonary hypertension
A new CT scan pulmonary angiography model may help optimize the diagnostic work-up process for patients with suspected pulmonary hypertension (PH), according to a recent study.
The diagnostic and prognostic utility of the model was validated in a tertiary referral population of treatment-naive patients who had a high pretest probability of PH.
“The aim of this study was to (a) build a diagnostic CT model in patients with suspected PH using the current guideline definition of PH (mPAP [mean pulmonary arterial pressure] ≥25 mm Hg) and the recent proposed definition of >20 mm Hg and (b) test its prognostic significance,” wrote Andrew J. Swift, MBChB, PhD, of the University of Sheffield (England) and colleagues in European Radiology.
The study cohort included 491 patients with suspected PH who underwent routine CT pulmonary angiography and right-heart catheterization between April 2012 and March 2016. CT metrics for patients with PH were developed using axial and reconstructed images.
The researchers identified the derivation (n = 247) and validation (n = 244) cohorts using random patient selection. In the derivation cohort, multivariate regression analysis was conducted to develop a model with the ability to predict mPAP ≥25 mm Hg and >20 mm Hg.
In the validation cohort, receiver operating characteristic analysis was performed to establish compromise CT thresholds, as well as sensitivity and specificity. The prognostic utility of the model was evaluated using Kaplan-Meier analysis.
Derivation cohort
Among the 247 patients in the derivation cohort, a CT regression model was identified, which included right-ventricle outflow tract thickness, main pulmonary artery diameter, and left ventricular area and interventricular septal angle; the area under the curve (AUC) in this cohort was 0.92.
Validation cohort
Among the 244 patients in the validation cohort, the model demonstrated strong diagnostic utility for the detection of PH, with an AUC of 0.91 and 0.94 for mPAP >20 mm Hg and ≥25 mm Hg, respectively.
With respect to the prognostic utility of the model, the researchers found that the diagnostic thresholds were prognostic in the CT model (all P < .01).
“The diagnostic CT thresholds are also of prognostic value; patients found not to have PH on CT have an excellent outcome,” they explained.
Dr. Swift and colleagues acknowledged that positive and negative predictive values will change based on the diagnostic setting. As a result, the findings from the current study may only be applicable to tertiary referral patient populations.
“This data may be particularly helpful when triaging patients with suspected severe PH for consideration of targeted pulmonary vascular therapies,” they concluded.
The study was supported by Wellcome Trust, the National Institute for Health Research, MRC POLARIS, and Bayer. The authors reported having no conflicts of interest with any companies related to the publication.
SOURCE: Swift AJ et al. Eur Radiol. 2020 Apr 27. doi: 10.1007/s00330-020-06846-1.
A new CT scan pulmonary angiography model may help optimize the diagnostic work-up process for patients with suspected pulmonary hypertension (PH), according to a recent study.
The diagnostic and prognostic utility of the model was validated in a tertiary referral population of treatment-naive patients who had a high pretest probability of PH.
“The aim of this study was to (a) build a diagnostic CT model in patients with suspected PH using the current guideline definition of PH (mPAP [mean pulmonary arterial pressure] ≥25 mm Hg) and the recent proposed definition of >20 mm Hg and (b) test its prognostic significance,” wrote Andrew J. Swift, MBChB, PhD, of the University of Sheffield (England) and colleagues in European Radiology.
The study cohort included 491 patients with suspected PH who underwent routine CT pulmonary angiography and right-heart catheterization between April 2012 and March 2016. CT metrics for patients with PH were developed using axial and reconstructed images.
The researchers identified the derivation (n = 247) and validation (n = 244) cohorts using random patient selection. In the derivation cohort, multivariate regression analysis was conducted to develop a model with the ability to predict mPAP ≥25 mm Hg and >20 mm Hg.
In the validation cohort, receiver operating characteristic analysis was performed to establish compromise CT thresholds, as well as sensitivity and specificity. The prognostic utility of the model was evaluated using Kaplan-Meier analysis.
Derivation cohort
Among the 247 patients in the derivation cohort, a CT regression model was identified, which included right-ventricle outflow tract thickness, main pulmonary artery diameter, and left ventricular area and interventricular septal angle; the area under the curve (AUC) in this cohort was 0.92.
Validation cohort
Among the 244 patients in the validation cohort, the model demonstrated strong diagnostic utility for the detection of PH, with an AUC of 0.91 and 0.94 for mPAP >20 mm Hg and ≥25 mm Hg, respectively.
With respect to the prognostic utility of the model, the researchers found that the diagnostic thresholds were prognostic in the CT model (all P < .01).
“The diagnostic CT thresholds are also of prognostic value; patients found not to have PH on CT have an excellent outcome,” they explained.
Dr. Swift and colleagues acknowledged that positive and negative predictive values will change based on the diagnostic setting. As a result, the findings from the current study may only be applicable to tertiary referral patient populations.
“This data may be particularly helpful when triaging patients with suspected severe PH for consideration of targeted pulmonary vascular therapies,” they concluded.
The study was supported by Wellcome Trust, the National Institute for Health Research, MRC POLARIS, and Bayer. The authors reported having no conflicts of interest with any companies related to the publication.
SOURCE: Swift AJ et al. Eur Radiol. 2020 Apr 27. doi: 10.1007/s00330-020-06846-1.
A new CT scan pulmonary angiography model may help optimize the diagnostic work-up process for patients with suspected pulmonary hypertension (PH), according to a recent study.
The diagnostic and prognostic utility of the model was validated in a tertiary referral population of treatment-naive patients who had a high pretest probability of PH.
“The aim of this study was to (a) build a diagnostic CT model in patients with suspected PH using the current guideline definition of PH (mPAP [mean pulmonary arterial pressure] ≥25 mm Hg) and the recent proposed definition of >20 mm Hg and (b) test its prognostic significance,” wrote Andrew J. Swift, MBChB, PhD, of the University of Sheffield (England) and colleagues in European Radiology.
The study cohort included 491 patients with suspected PH who underwent routine CT pulmonary angiography and right-heart catheterization between April 2012 and March 2016. CT metrics for patients with PH were developed using axial and reconstructed images.
The researchers identified the derivation (n = 247) and validation (n = 244) cohorts using random patient selection. In the derivation cohort, multivariate regression analysis was conducted to develop a model with the ability to predict mPAP ≥25 mm Hg and >20 mm Hg.
In the validation cohort, receiver operating characteristic analysis was performed to establish compromise CT thresholds, as well as sensitivity and specificity. The prognostic utility of the model was evaluated using Kaplan-Meier analysis.
Derivation cohort
Among the 247 patients in the derivation cohort, a CT regression model was identified, which included right-ventricle outflow tract thickness, main pulmonary artery diameter, and left ventricular area and interventricular septal angle; the area under the curve (AUC) in this cohort was 0.92.
Validation cohort
Among the 244 patients in the validation cohort, the model demonstrated strong diagnostic utility for the detection of PH, with an AUC of 0.91 and 0.94 for mPAP >20 mm Hg and ≥25 mm Hg, respectively.
With respect to the prognostic utility of the model, the researchers found that the diagnostic thresholds were prognostic in the CT model (all P < .01).
“The diagnostic CT thresholds are also of prognostic value; patients found not to have PH on CT have an excellent outcome,” they explained.
Dr. Swift and colleagues acknowledged that positive and negative predictive values will change based on the diagnostic setting. As a result, the findings from the current study may only be applicable to tertiary referral patient populations.
“This data may be particularly helpful when triaging patients with suspected severe PH for consideration of targeted pulmonary vascular therapies,” they concluded.
The study was supported by Wellcome Trust, the National Institute for Health Research, MRC POLARIS, and Bayer. The authors reported having no conflicts of interest with any companies related to the publication.
SOURCE: Swift AJ et al. Eur Radiol. 2020 Apr 27. doi: 10.1007/s00330-020-06846-1.
FROM EUROPEAN RADIOLOGY