HT Staff

Crowded street

Photo by Pavel Novak

VIENNA—Living in overcrowded conditions may affect a young person’s risk of developing certain subtypes of Hodgkin lymphoma (HL), according to researchers.

They studied more than 600 children and young adults with HL in England and found that patients who lived in areas with more overcrowded households had a lower incidence of nodular sclerosis (NS) HL but a higher incidence of the not-otherwise-specified (NOS) subtype of HL.

“Our findings related to the NS subtype may suggest that the recurrent infections to which children living in overcrowded conditions are likely to have been exposed stimulate their immune systems and, hence, protect them against developing this type of cancer later in their childhood and early adult life,” said Richard McNally, PhD, of Newcastle University in the UK.

“Those who have a genetic susceptibility to HL and have been less exposed to infection through not living in such overcrowded conditions may have less developed immune systems as a result and are therefore at greater risk of developing this subtype.”

Dr McNally and his colleagues added that it’s more difficult to interpret the findings in the NOS group because this subtype of HL is very heterogeneous. The team said the role of chance cannot be ruled out.

They presented this research at the 2015 European Cancer Congress (abstract 1414).

Dr McNally and his colleagues wanted to gain a better understanding of factors that cause HL, so they analyzed a cohort of young HL patients in Northern England, looking at factors such as sex, age, and socio-economic deprivation.

The researchers evaluated 621 cases of HL recorded in the Northern Region Young Persons’ Malignant Disease Registry. Patients were ages 0 to 24 at diagnosis and were diagnosed between 1968 and 2003.

There were 5 different subtypes of HL in this group:

• 247 cases of the NS type
• 143 NOS
• 105 of mixed cellularity
• 58 lymphocyte-rich cases
• 68 “others.”

Age and sex

Overall, more males than females had HL, but the male-female ratio varied by both age group and subtype. The age-standardized rate (ASR) of HL for males was 18.15 per million persons per year, and the ASR for females was 10.52 per million persons per year.

For the NS subtype, there were 130 males and 117 females, but this was reversed at ages 20 to 24, with 72 females and 55 males. The ASR for NS HL at 20 to 24 was 14.26 for males and 18.79 for females.

“That this change takes place after puberty seems to suggest that estrogens may be responsible in some way,” Dr McNally said. “There are a lot of genes directly regulated by sex hormones, and they are obvious suspects. Alternatively, epigenetic changes . . .  influencing key genes, induced by sex hormones, may be responsible.”

Overcrowding

The researchers calculated socio-economic deprivation using the 4 components of the Townsend deprivation score: household overcrowding, non-home ownership, unemployment, and households with no car.

They observed a lower incidence of NS HL among those patients living in areas with more overcrowded households. The relative risk of NS HL was 0.88 for a 1% increase in household overcrowding (P<0.001).

For the NOS subtype, the reverse was seen. A 1% increase in household overcrowding was associated with an increased incidence of NOS HL—a relative risk of 1.17.

Overcrowding seemed to have no effect on the incidence of mixed-cellularity HL or lymphocyte-rich HL.

“We knew already that recurrent infections may protect against childhood leukemia, and now it looks as we can add Hodgkin lymphoma and, particularly its NS subtype, to the list,” Dr McNally said. “In order to further investigate the factors involved, prospective studies should investigate the hormonal changes and recurrent infections and their direct link to the risk of lymphoma, but such studies are difficult to do in rare diseases.”

“A practical follow-up would be case-control studies examining biological markers related to exposure to a multitude of infectious agents, and indeed to hormonal status itself, while genetic studies are another possibility.”

Crowded street

Photo by Pavel Novak

VIENNA—Living in overcrowded conditions may affect a young person’s risk of developing certain subtypes of Hodgkin lymphoma (HL), according to researchers.

They studied more than 600 children and young adults with HL in England and found that patients who lived in areas with more overcrowded households had a lower incidence of nodular sclerosis (NS) HL but a higher incidence of the not-otherwise-specified (NOS) subtype of HL.

“Our findings related to the NS subtype may suggest that the recurrent infections to which children living in overcrowded conditions are likely to have been exposed stimulate their immune systems and, hence, protect them against developing this type of cancer later in their childhood and early adult life,” said Richard McNally, PhD, of Newcastle University in the UK.

“Those who have a genetic susceptibility to HL and have been less exposed to infection through not living in such overcrowded conditions may have less developed immune systems as a result and are therefore at greater risk of developing this subtype.”

Dr McNally and his colleagues added that it’s more difficult to interpret the findings in the NOS group because this subtype of HL is very heterogeneous. The team said the role of chance cannot be ruled out.

They presented this research at the 2015 European Cancer Congress (abstract 1414).

Dr McNally and his colleagues wanted to gain a better understanding of factors that cause HL, so they analyzed a cohort of young HL patients in Northern England, looking at factors such as sex, age, and socio-economic deprivation.

The researchers evaluated 621 cases of HL recorded in the Northern Region Young Persons’ Malignant Disease Registry. Patients were ages 0 to 24 at diagnosis and were diagnosed between 1968 and 2003.

There were 5 different subtypes of HL in this group:

• 247 cases of the NS type
• 143 NOS
• 105 of mixed cellularity
• 58 lymphocyte-rich cases
• 68 “others.”

Age and sex

Overall, more males than females had HL, but the male-female ratio varied by both age group and subtype. The age-standardized rate (ASR) of HL for males was 18.15 per million persons per year, and the ASR for females was 10.52 per million persons per year.

For the NS subtype, there were 130 males and 117 females, but this was reversed at ages 20 to 24, with 72 females and 55 males. The ASR for NS HL at 20 to 24 was 14.26 for males and 18.79 for females.

“That this change takes place after puberty seems to suggest that estrogens may be responsible in some way,” Dr McNally said. “There are a lot of genes directly regulated by sex hormones, and they are obvious suspects. Alternatively, epigenetic changes . . .  influencing key genes, induced by sex hormones, may be responsible.”

Overcrowding

The researchers calculated socio-economic deprivation using the 4 components of the Townsend deprivation score: household overcrowding, non-home ownership, unemployment, and households with no car.

They observed a lower incidence of NS HL among those patients living in areas with more overcrowded households. The relative risk of NS HL was 0.88 for a 1% increase in household overcrowding (P<0.001).

For the NOS subtype, the reverse was seen. A 1% increase in household overcrowding was associated with an increased incidence of NOS HL—a relative risk of 1.17.

Overcrowding seemed to have no effect on the incidence of mixed-cellularity HL or lymphocyte-rich HL.

“We knew already that recurrent infections may protect against childhood leukemia, and now it looks as we can add Hodgkin lymphoma and, particularly its NS subtype, to the list,” Dr McNally said. “In order to further investigate the factors involved, prospective studies should investigate the hormonal changes and recurrent infections and their direct link to the risk of lymphoma, but such studies are difficult to do in rare diseases.”

“A practical follow-up would be case-control studies examining biological markers related to exposure to a multitude of infectious agents, and indeed to hormonal status itself, while genetic studies are another possibility.”

Crowded street

Photo by Pavel Novak

VIENNA—Living in overcrowded conditions may affect a young person’s risk of developing certain subtypes of Hodgkin lymphoma (HL), according to researchers.

They studied more than 600 children and young adults with HL in England and found that patients who lived in areas with more overcrowded households had a lower incidence of nodular sclerosis (NS) HL but a higher incidence of the not-otherwise-specified (NOS) subtype of HL.

“Our findings related to the NS subtype may suggest that the recurrent infections to which children living in overcrowded conditions are likely to have been exposed stimulate their immune systems and, hence, protect them against developing this type of cancer later in their childhood and early adult life,” said Richard McNally, PhD, of Newcastle University in the UK.

“Those who have a genetic susceptibility to HL and have been less exposed to infection through not living in such overcrowded conditions may have less developed immune systems as a result and are therefore at greater risk of developing this subtype.”

Dr McNally and his colleagues added that it’s more difficult to interpret the findings in the NOS group because this subtype of HL is very heterogeneous. The team said the role of chance cannot be ruled out.

They presented this research at the 2015 European Cancer Congress (abstract 1414).

Dr McNally and his colleagues wanted to gain a better understanding of factors that cause HL, so they analyzed a cohort of young HL patients in Northern England, looking at factors such as sex, age, and socio-economic deprivation.

The researchers evaluated 621 cases of HL recorded in the Northern Region Young Persons’ Malignant Disease Registry. Patients were ages 0 to 24 at diagnosis and were diagnosed between 1968 and 2003.

There were 5 different subtypes of HL in this group:

• 247 cases of the NS type
• 143 NOS
• 105 of mixed cellularity
• 58 lymphocyte-rich cases
• 68 “others.”

Age and sex

Overall, more males than females had HL, but the male-female ratio varied by both age group and subtype. The age-standardized rate (ASR) of HL for males was 18.15 per million persons per year, and the ASR for females was 10.52 per million persons per year.

For the NS subtype, there were 130 males and 117 females, but this was reversed at ages 20 to 24, with 72 females and 55 males. The ASR for NS HL at 20 to 24 was 14.26 for males and 18.79 for females.

“That this change takes place after puberty seems to suggest that estrogens may be responsible in some way,” Dr McNally said. “There are a lot of genes directly regulated by sex hormones, and they are obvious suspects. Alternatively, epigenetic changes . . .  influencing key genes, induced by sex hormones, may be responsible.”

Overcrowding

The researchers calculated socio-economic deprivation using the 4 components of the Townsend deprivation score: household overcrowding, non-home ownership, unemployment, and households with no car.

They observed a lower incidence of NS HL among those patients living in areas with more overcrowded households. The relative risk of NS HL was 0.88 for a 1% increase in household overcrowding (P<0.001).

For the NOS subtype, the reverse was seen. A 1% increase in household overcrowding was associated with an increased incidence of NOS HL—a relative risk of 1.17.

Overcrowding seemed to have no effect on the incidence of mixed-cellularity HL or lymphocyte-rich HL.

“We knew already that recurrent infections may protect against childhood leukemia, and now it looks as we can add Hodgkin lymphoma and, particularly its NS subtype, to the list,” Dr McNally said. “In order to further investigate the factors involved, prospective studies should investigate the hormonal changes and recurrent infections and their direct link to the risk of lymphoma, but such studies are difficult to do in rare diseases.”

“A practical follow-up would be case-control studies examining biological markers related to exposure to a multitude of infectious agents, and indeed to hormonal status itself, while genetic studies are another possibility.”

Monoclonal antibodies

Photo by Linda Bartlett

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has agreed to provide accelerated assessment for daratumumab.

The drug is under review as monotherapy for patients with relapsed and refractory multiple myeloma (MM).

The CHMP grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.

Accelerated assessment shortens the review period from 210 days to 150 days.

About daratumumab

Daratumumab is an investigational monoclonal antibody that works by binding to CD38 on the surface of MM cells. In doing so, daratumumab triggers the patient’s own immune system to attack MM cells, resulting in cell death through multiple mechanisms of action.

In July 2013, daratumumab was granted orphan drug status by the European Medicines Agency for the treatment of plasma cell myeloma.

The drug has been accepted for priority review in the US as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

In August 2012, Janssen Biotech, Inc. and Genmab entered an agreement that granted Janssen an exclusive worldwide license to develop, manufacture, and commercialize daratumumab.

Daratumumab trials

The marketing authorization application for daratumumab includes data from the phase 2 MMY2002 (SIRIUS) study, the phase 1/2 GEN501 study, and 3 additional supportive studies.

The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.

The results suggested that daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%.

Most adverse events in this study were grade 1 or 2, although serious events did occur.

The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 of the patients received the drug at 16 mg/kg.

Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.

Monoclonal antibodies

Photo by Linda Bartlett

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has agreed to provide accelerated assessment for daratumumab.

The drug is under review as monotherapy for patients with relapsed and refractory multiple myeloma (MM).

The CHMP grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.

Accelerated assessment shortens the review period from 210 days to 150 days.

About daratumumab

Daratumumab is an investigational monoclonal antibody that works by binding to CD38 on the surface of MM cells. In doing so, daratumumab triggers the patient’s own immune system to attack MM cells, resulting in cell death through multiple mechanisms of action.

In July 2013, daratumumab was granted orphan drug status by the European Medicines Agency for the treatment of plasma cell myeloma.

The drug has been accepted for priority review in the US as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

In August 2012, Janssen Biotech, Inc. and Genmab entered an agreement that granted Janssen an exclusive worldwide license to develop, manufacture, and commercialize daratumumab.

Daratumumab trials

The marketing authorization application for daratumumab includes data from the phase 2 MMY2002 (SIRIUS) study, the phase 1/2 GEN501 study, and 3 additional supportive studies.

The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.

The results suggested that daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%.

Most adverse events in this study were grade 1 or 2, although serious events did occur.

The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 of the patients received the drug at 16 mg/kg.

Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.

Monoclonal antibodies

Photo by Linda Bartlett

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has agreed to provide accelerated assessment for daratumumab.

The drug is under review as monotherapy for patients with relapsed and refractory multiple myeloma (MM).

The CHMP grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.

Accelerated assessment shortens the review period from 210 days to 150 days.

About daratumumab

Daratumumab is an investigational monoclonal antibody that works by binding to CD38 on the surface of MM cells. In doing so, daratumumab triggers the patient’s own immune system to attack MM cells, resulting in cell death through multiple mechanisms of action.

In July 2013, daratumumab was granted orphan drug status by the European Medicines Agency for the treatment of plasma cell myeloma.

The drug has been accepted for priority review in the US as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

In August 2012, Janssen Biotech, Inc. and Genmab entered an agreement that granted Janssen an exclusive worldwide license to develop, manufacture, and commercialize daratumumab.

Daratumumab trials

The marketing authorization application for daratumumab includes data from the phase 2 MMY2002 (SIRIUS) study, the phase 1/2 GEN501 study, and 3 additional supportive studies.

The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.

The results suggested that daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%.

Most adverse events in this study were grade 1 or 2, although serious events did occur.

The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 of the patients received the drug at 16 mg/kg.

Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.

Children from a village

outside of Nairobi, Kenya

Photo by Gabrielle Tenenbaum

Researchers say they have identified genetic variants that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the disease.

The variants are at a locus located next to a cluster of genes that are responsible for creating the receptors the malaria parasite Plasmodium falciparum uses to infect red blood cells.

The researchers described their findings in a letter to Nature.

“The risk of developing severe malaria turns out to be strongly linked to the process by which the malaria parasite gains entry to the human red blood cell,” said Dr Kevin Marsh, of the Kemri-Wellcome Research Programme in Kilifi, Kenya.

“This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.”

For this study, Dr Marsh and his colleagues analyzed data from 8 different African countries: Burkina Faso, Cameroon, Ghana, Kenya, Malawi, Mali, The Gambia, and Tanzania.

They compared the DNA of 5633 children with severe malaria and the DNA of 5919 children without severe malaria. The researchers then replicated their key findings in a further 14,000 children.

The locus the team identified is near a cluster of genes that code for glycophorins, which are involved in P falciparum’s invasion of red blood cells.

The researchers also found an allele that was common among children in Kenya. Having this allele reduced the risk of severe malaria by about 40% in Kenyan children, with a slightly smaller effect across all the other populations studied.

The team said this difference between populations could be due to the genetic features of the local malaria parasite in East Africa.

Balancing selection

The newly identified malaria resistance locus lies within a region of the genome where humans and chimpanzees have been known to share particular combinations of haplotypes.

This indicates that some of the variation seen in contemporary humans has been present for millions of years. The finding also suggests that this region of the genome is the subject of balancing selection.

Balancing selection happens when a particular genetic variant evolves because it confers health benefits, but it is carried by only a proportion of the population because it also has damaging consequences.

“These findings indicate that balancing selection and resistance to malaria are deeply intertwined themes in our ancient evolutionary history,” said Dr Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“This new resistance locus is particularly interesting because it lies so close to genes that are gatekeepers for the malaria parasite’s invasion machinery. We now need to drill down at this locus to characterize these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act.”

Children from a village

outside of Nairobi, Kenya

Photo by Gabrielle Tenenbaum

Researchers say they have identified genetic variants that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the disease.

The variants are at a locus located next to a cluster of genes that are responsible for creating the receptors the malaria parasite Plasmodium falciparum uses to infect red blood cells.

The researchers described their findings in a letter to Nature.

“The risk of developing severe malaria turns out to be strongly linked to the process by which the malaria parasite gains entry to the human red blood cell,” said Dr Kevin Marsh, of the Kemri-Wellcome Research Programme in Kilifi, Kenya.

“This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.”

For this study, Dr Marsh and his colleagues analyzed data from 8 different African countries: Burkina Faso, Cameroon, Ghana, Kenya, Malawi, Mali, The Gambia, and Tanzania.

They compared the DNA of 5633 children with severe malaria and the DNA of 5919 children without severe malaria. The researchers then replicated their key findings in a further 14,000 children.

The locus the team identified is near a cluster of genes that code for glycophorins, which are involved in P falciparum’s invasion of red blood cells.

The researchers also found an allele that was common among children in Kenya. Having this allele reduced the risk of severe malaria by about 40% in Kenyan children, with a slightly smaller effect across all the other populations studied.

The team said this difference between populations could be due to the genetic features of the local malaria parasite in East Africa.

Balancing selection

The newly identified malaria resistance locus lies within a region of the genome where humans and chimpanzees have been known to share particular combinations of haplotypes.

This indicates that some of the variation seen in contemporary humans has been present for millions of years. The finding also suggests that this region of the genome is the subject of balancing selection.

Balancing selection happens when a particular genetic variant evolves because it confers health benefits, but it is carried by only a proportion of the population because it also has damaging consequences.

“These findings indicate that balancing selection and resistance to malaria are deeply intertwined themes in our ancient evolutionary history,” said Dr Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“This new resistance locus is particularly interesting because it lies so close to genes that are gatekeepers for the malaria parasite’s invasion machinery. We now need to drill down at this locus to characterize these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act.”

Children from a village

outside of Nairobi, Kenya

Photo by Gabrielle Tenenbaum

Researchers say they have identified genetic variants that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the disease.

The variants are at a locus located next to a cluster of genes that are responsible for creating the receptors the malaria parasite Plasmodium falciparum uses to infect red blood cells.

The researchers described their findings in a letter to Nature.

“The risk of developing severe malaria turns out to be strongly linked to the process by which the malaria parasite gains entry to the human red blood cell,” said Dr Kevin Marsh, of the Kemri-Wellcome Research Programme in Kilifi, Kenya.

“This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.”

For this study, Dr Marsh and his colleagues analyzed data from 8 different African countries: Burkina Faso, Cameroon, Ghana, Kenya, Malawi, Mali, The Gambia, and Tanzania.

They compared the DNA of 5633 children with severe malaria and the DNA of 5919 children without severe malaria. The researchers then replicated their key findings in a further 14,000 children.

The locus the team identified is near a cluster of genes that code for glycophorins, which are involved in P falciparum’s invasion of red blood cells.

The researchers also found an allele that was common among children in Kenya. Having this allele reduced the risk of severe malaria by about 40% in Kenyan children, with a slightly smaller effect across all the other populations studied.

The team said this difference between populations could be due to the genetic features of the local malaria parasite in East Africa.

Balancing selection

The newly identified malaria resistance locus lies within a region of the genome where humans and chimpanzees have been known to share particular combinations of haplotypes.

This indicates that some of the variation seen in contemporary humans has been present for millions of years. The finding also suggests that this region of the genome is the subject of balancing selection.

Balancing selection happens when a particular genetic variant evolves because it confers health benefits, but it is carried by only a proportion of the population because it also has damaging consequences.

“These findings indicate that balancing selection and resistance to malaria are deeply intertwined themes in our ancient evolutionary history,” said Dr Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“This new resistance locus is particularly interesting because it lies so close to genes that are gatekeepers for the malaria parasite’s invasion machinery. We now need to drill down at this locus to characterize these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act.”

Blood samples

Photo by Graham Colm

New research has revealed a microRNA (miRNA) signature in the bone marrow of patients with multiple myeloma (MM) that is also detectable in peripheral blood.

Investigators believe this signature may mark the onset of MM and predict progression to MM in patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM).

This research has been published in The Journal of Molecular Diagnostics.

“Currently, there is no single factor that can predict patients with MGUS or SMM who are likely to progress to myeloma,” said Katherine R. Calvo, MD, PhD, of the National Institutes of Health in Bethesda, Maryland.

“A biomarker of disease progression in the peripheral blood could assist in the early identification of patients evolving to multiple myeloma.”

With this in mind, Dr Calvo and her colleagues studied miRNAs as possible biomarkers of MM. Previous research has shown increased levels of specific miRNAs in the blood and plasma of MM patients.

In this study, the investigators analyzed bone marrow, plasma, and serum samples from healthy controls and patients with MM, MGUS, or SMM.

The team analyzed fluid from the bone marrow of 20 patients with MM and identified 111 miRNAs that showed a 2-fold or greater difference from levels observed in 8 control samples. Sixty-nine of the miRNAs were downregulated, and 42 were upregulated.

Further analysis revealed a unique miRNA signature indicative of MM. The bone marrow signature included 8 members of the let-7 family of miRNAs, each of which showed significant decreases ranging from 6-fold to 17-fold (P<0.03) in patients with MM.

Other experiments revealed the miRNA profiles characteristic of MM in peripheral blood, serum, and plasma samples.

Using quantitative real-time PCR, the investigators identified 18 miRNAs that were significantly decreased in bone marrow MM samples. Of these, 11 (60%) miRNAs were also significantly decreased in serum samples, and 6 of the 11 were also found to be lower in plasma samples (including 3 members of the let-7 miRNA family).

The investigators further explored whether the miRNA pattern of MM in precursor diseases changes as the disease progresses. They analyzed serum samples in 17 patients with MGUS, 17 with SMM, 13 with MM, and 12 healthy controls.

Only 4 of the 11 miRNAs (36%) that were reduced in the MM serum samples were lower in the MGUS samples.

“This suggests that aberrant expression of these [4] miRNAs may be associated with early events in plasma cell neoplasia,” Dr Calvo said.

Eight of the 11 (73%) miRNAs were decreased in SMM plasma samples. However, 3 (27%) were significantly reduced only in the MM samples, suggesting that downregulation of this group of miRNAs may be related to later events during evolution from precursor disease to MM.

“Our findings suggest that the antiproliferative and proapoptotic miRNAs, such as the let-7 family members, are downregulated in multiple myeloma’s microenvironment,” Dr Calvo said.

“These findings suggest that measuring expression of miRNAs associated with myeloma progression in the peripheral blood may hold promise for predicting disease progression in MGUS and SMM.”

Blood samples

Photo by Graham Colm

New research has revealed a microRNA (miRNA) signature in the bone marrow of patients with multiple myeloma (MM) that is also detectable in peripheral blood.

Investigators believe this signature may mark the onset of MM and predict progression to MM in patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM).

This research has been published in The Journal of Molecular Diagnostics.

“Currently, there is no single factor that can predict patients with MGUS or SMM who are likely to progress to myeloma,” said Katherine R. Calvo, MD, PhD, of the National Institutes of Health in Bethesda, Maryland.

“A biomarker of disease progression in the peripheral blood could assist in the early identification of patients evolving to multiple myeloma.”

With this in mind, Dr Calvo and her colleagues studied miRNAs as possible biomarkers of MM. Previous research has shown increased levels of specific miRNAs in the blood and plasma of MM patients.

In this study, the investigators analyzed bone marrow, plasma, and serum samples from healthy controls and patients with MM, MGUS, or SMM.

The team analyzed fluid from the bone marrow of 20 patients with MM and identified 111 miRNAs that showed a 2-fold or greater difference from levels observed in 8 control samples. Sixty-nine of the miRNAs were downregulated, and 42 were upregulated.

Further analysis revealed a unique miRNA signature indicative of MM. The bone marrow signature included 8 members of the let-7 family of miRNAs, each of which showed significant decreases ranging from 6-fold to 17-fold (P<0.03) in patients with MM.

Other experiments revealed the miRNA profiles characteristic of MM in peripheral blood, serum, and plasma samples.

Using quantitative real-time PCR, the investigators identified 18 miRNAs that were significantly decreased in bone marrow MM samples. Of these, 11 (60%) miRNAs were also significantly decreased in serum samples, and 6 of the 11 were also found to be lower in plasma samples (including 3 members of the let-7 miRNA family).

The investigators further explored whether the miRNA pattern of MM in precursor diseases changes as the disease progresses. They analyzed serum samples in 17 patients with MGUS, 17 with SMM, 13 with MM, and 12 healthy controls.

Only 4 of the 11 miRNAs (36%) that were reduced in the MM serum samples were lower in the MGUS samples.

“This suggests that aberrant expression of these [4] miRNAs may be associated with early events in plasma cell neoplasia,” Dr Calvo said.

Eight of the 11 (73%) miRNAs were decreased in SMM plasma samples. However, 3 (27%) were significantly reduced only in the MM samples, suggesting that downregulation of this group of miRNAs may be related to later events during evolution from precursor disease to MM.

“Our findings suggest that the antiproliferative and proapoptotic miRNAs, such as the let-7 family members, are downregulated in multiple myeloma’s microenvironment,” Dr Calvo said.

“These findings suggest that measuring expression of miRNAs associated with myeloma progression in the peripheral blood may hold promise for predicting disease progression in MGUS and SMM.”

Blood samples

Photo by Graham Colm

New research has revealed a microRNA (miRNA) signature in the bone marrow of patients with multiple myeloma (MM) that is also detectable in peripheral blood.

Investigators believe this signature may mark the onset of MM and predict progression to MM in patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM).

This research has been published in The Journal of Molecular Diagnostics.

“Currently, there is no single factor that can predict patients with MGUS or SMM who are likely to progress to myeloma,” said Katherine R. Calvo, MD, PhD, of the National Institutes of Health in Bethesda, Maryland.

“A biomarker of disease progression in the peripheral blood could assist in the early identification of patients evolving to multiple myeloma.”

With this in mind, Dr Calvo and her colleagues studied miRNAs as possible biomarkers of MM. Previous research has shown increased levels of specific miRNAs in the blood and plasma of MM patients.

In this study, the investigators analyzed bone marrow, plasma, and serum samples from healthy controls and patients with MM, MGUS, or SMM.

The team analyzed fluid from the bone marrow of 20 patients with MM and identified 111 miRNAs that showed a 2-fold or greater difference from levels observed in 8 control samples. Sixty-nine of the miRNAs were downregulated, and 42 were upregulated.

Further analysis revealed a unique miRNA signature indicative of MM. The bone marrow signature included 8 members of the let-7 family of miRNAs, each of which showed significant decreases ranging from 6-fold to 17-fold (P<0.03) in patients with MM.

Other experiments revealed the miRNA profiles characteristic of MM in peripheral blood, serum, and plasma samples.

Using quantitative real-time PCR, the investigators identified 18 miRNAs that were significantly decreased in bone marrow MM samples. Of these, 11 (60%) miRNAs were also significantly decreased in serum samples, and 6 of the 11 were also found to be lower in plasma samples (including 3 members of the let-7 miRNA family).

The investigators further explored whether the miRNA pattern of MM in precursor diseases changes as the disease progresses. They analyzed serum samples in 17 patients with MGUS, 17 with SMM, 13 with MM, and 12 healthy controls.

Only 4 of the 11 miRNAs (36%) that were reduced in the MM serum samples were lower in the MGUS samples.

“This suggests that aberrant expression of these [4] miRNAs may be associated with early events in plasma cell neoplasia,” Dr Calvo said.

Eight of the 11 (73%) miRNAs were decreased in SMM plasma samples. However, 3 (27%) were significantly reduced only in the MM samples, suggesting that downregulation of this group of miRNAs may be related to later events during evolution from precursor disease to MM.

“Our findings suggest that the antiproliferative and proapoptotic miRNAs, such as the let-7 family members, are downregulated in multiple myeloma’s microenvironment,” Dr Calvo said.

“These findings suggest that measuring expression of miRNAs associated with myeloma progression in the peripheral blood may hold promise for predicting disease progression in MGUS and SMM.”

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to

deliver its final decision within 3 months.

If approved by the EC, efmoroctocog alfa would be the first hemophilia A treatment with prolonged circulation available in the European Union (plus Iceland, Lichtenstein, and Norway).

The CHMP’s positive opinion of efmoroctocog alfa was based on results from 2 phase 3 studies—A-LONG and Kids A-LONG.

A-LONG

The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.

Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.

None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with rFVIII.

Kids A-LONG

The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to FVIII therapies.

The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.

None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.

ASPIRE

Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.

Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.

Efmoroctocog alfa development

Elocta is the European trade name for efmoroctocog alfa, which is known as Eloctate in the US, Canada, Australia, New Zealand, and Japan, where it is approved for the treatment of hemophilia A.

Biogen and Sobi are collaboration partners in the development and commercialization of efmoroctocog alfa for hemophilia A.

Last year, Sobi exercised its opt-in right to assume final development and commercialization of efmoroctocog alfa in the Sobi territories (essentially, Europe, North Africa, Russia, and certain countries in the Middle East). Biogen leads development for efmoroctocog alfa, has manufacturing rights, and has commercialization rights in North America and all other regions in the world excluding the Sobi territories.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to

deliver its final decision within 3 months.

If approved by the EC, efmoroctocog alfa would be the first hemophilia A treatment with prolonged circulation available in the European Union (plus Iceland, Lichtenstein, and Norway).

The CHMP’s positive opinion of efmoroctocog alfa was based on results from 2 phase 3 studies—A-LONG and Kids A-LONG.

A-LONG

The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.

Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.

None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with rFVIII.

Kids A-LONG

The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to FVIII therapies.

The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.

None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.

ASPIRE

Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.

Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.

Efmoroctocog alfa development

Elocta is the European trade name for efmoroctocog alfa, which is known as Eloctate in the US, Canada, Australia, New Zealand, and Japan, where it is approved for the treatment of hemophilia A.

Biogen and Sobi are collaboration partners in the development and commercialization of efmoroctocog alfa for hemophilia A.

Last year, Sobi exercised its opt-in right to assume final development and commercialization of efmoroctocog alfa in the Sobi territories (essentially, Europe, North Africa, Russia, and certain countries in the Middle East). Biogen leads development for efmoroctocog alfa, has manufacturing rights, and has commercialization rights in North America and all other regions in the world excluding the Sobi territories.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to

deliver its final decision within 3 months.

If approved by the EC, efmoroctocog alfa would be the first hemophilia A treatment with prolonged circulation available in the European Union (plus Iceland, Lichtenstein, and Norway).

The CHMP’s positive opinion of efmoroctocog alfa was based on results from 2 phase 3 studies—A-LONG and Kids A-LONG.

A-LONG

The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.

Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.

None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with rFVIII.

Kids A-LONG

The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to FVIII therapies.

The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.

None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.

ASPIRE

Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.

Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.

Efmoroctocog alfa development

Elocta is the European trade name for efmoroctocog alfa, which is known as Eloctate in the US, Canada, Australia, New Zealand, and Japan, where it is approved for the treatment of hemophilia A.

Biogen and Sobi are collaboration partners in the development and commercialization of efmoroctocog alfa for hemophilia A.

Last year, Sobi exercised its opt-in right to assume final development and commercialization of efmoroctocog alfa in the Sobi territories (essentially, Europe, North Africa, Russia, and certain countries in the Middle East). Biogen leads development for efmoroctocog alfa, has manufacturing rights, and has commercialization rights in North America and all other regions in the world excluding the Sobi territories.

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

VIENNA—Millions of people throughout the world are dying from potentially treatable cancers because of a chronic underinvestment in radiotherapy resources, according to a new report.

The report suggests that expanding access to radiotherapy services will require a sizeable investment upfront, but that investment could bring economic benefits of up to $365 billion in developing countries over the next 20 years.

The report was published in The Lancet Oncology and presented at the 2015 European Cancer Congress.

The report estimates that 204 million fractions of radiotherapy will be needed to treat the 12 million cancer patients worldwide who could benefit from treatment in 2035.

But the cost per fraction is highly cost-effective and low compared to the price of many new cancer drugs, according to the report’s authors.

They estimate that full access to radiotherapy could be achieved for all patients in need in low-and middle income countries (LMIC) by 2035 for $97 billion, with potential health benefits of 27 million life-years saved and economic benefits ranging from $278 billion to $365 billion over the next 20 years.

“There is a widespread misconception that the costs of providing radiotherapy put it beyond the reach of all but the richest countries, [but] nothing could be further from the truth,” said Rifat Atun, MBBS, of Harvard University in Boston, Massachusetts.

“Our work . . .  clearly shows that not only can this essential service be deployed safely and high quality treatment delivered in low- and middle-income countries, but that scale-up of radiotherapy capacity is a feasible and highly cost-effective investment.”

The report provides details on access to radiotherapy services across the world, on a country-by-country basis. The authors calculated the costs and benefits of meeting the worldwide shortfall in resources and bridging the gap in access to effective treatment.

Estimates suggest that, at present, about 40% to 60% of cancer patients worldwide have access to radiotherapy. Even in high-income countries like Canada, Australia, and the UK, numbers of radiotherapy facilities, equipment, and trained staff are inadequate.

Access is worst in low-income countries, where as many as 9 out of 10 people cannot access radiotherapy. The problem of access is especially acute in Africa. In most African countries, radiotherapy is virtually non-existent. Forty countries have no radiotherapy facilities at all.

“The time has come to agree and implement immediate actions to tackle the global shortfall in radiotherapy services and the crisis of access to this highly effective treatment,” Dr Atun said.

With that in mind, he and his colleagues called for the following 6 targets to be met.

By 2020:

• 80% of countries to have comprehensive cancer plans that include radiotherapy.
• Each LMIC to create 1 new center for treatment and training.
• 80% of LMICs to include radiotherapy services in their universal health coverage plans.

By 2025:

• A 25% increase in radiotherapy treatment capacity.
• LMICs to train 7500 radiation oncologists, 20,000 radiotherapy radiographers, and 6000 medical physicists.
• $46 billion of upfront investment to be raised to establish radiotherapy infrastructure and training in LMICs (with help from international banks and the private sector).

“The evidence outlined in the [report] reinforces the case for investing in radiotherapy as an essential component of cancer control,” said Mary Gospodarowicz, MD, co-chair of the UICC Global Task Force on Radiotherapy for Cancer Control.

“The building of radiotherapy capacity will require large initial investment. However, the treatment is more cost-effective than chemotherapy and surgery for treating cancer, and the health and economic benefits will be realized in just 10 to 15 years.”

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

VIENNA—Millions of people throughout the world are dying from potentially treatable cancers because of a chronic underinvestment in radiotherapy resources, according to a new report.

The report suggests that expanding access to radiotherapy services will require a sizeable investment upfront, but that investment could bring economic benefits of up to $365 billion in developing countries over the next 20 years.

The report was published in The Lancet Oncology and presented at the 2015 European Cancer Congress.

The report estimates that 204 million fractions of radiotherapy will be needed to treat the 12 million cancer patients worldwide who could benefit from treatment in 2035.

But the cost per fraction is highly cost-effective and low compared to the price of many new cancer drugs, according to the report’s authors.

They estimate that full access to radiotherapy could be achieved for all patients in need in low-and middle income countries (LMIC) by 2035 for $97 billion, with potential health benefits of 27 million life-years saved and economic benefits ranging from $278 billion to $365 billion over the next 20 years.

“There is a widespread misconception that the costs of providing radiotherapy put it beyond the reach of all but the richest countries, [but] nothing could be further from the truth,” said Rifat Atun, MBBS, of Harvard University in Boston, Massachusetts.

“Our work . . .  clearly shows that not only can this essential service be deployed safely and high quality treatment delivered in low- and middle-income countries, but that scale-up of radiotherapy capacity is a feasible and highly cost-effective investment.”

The report provides details on access to radiotherapy services across the world, on a country-by-country basis. The authors calculated the costs and benefits of meeting the worldwide shortfall in resources and bridging the gap in access to effective treatment.

Estimates suggest that, at present, about 40% to 60% of cancer patients worldwide have access to radiotherapy. Even in high-income countries like Canada, Australia, and the UK, numbers of radiotherapy facilities, equipment, and trained staff are inadequate.

Access is worst in low-income countries, where as many as 9 out of 10 people cannot access radiotherapy. The problem of access is especially acute in Africa. In most African countries, radiotherapy is virtually non-existent. Forty countries have no radiotherapy facilities at all.

“The time has come to agree and implement immediate actions to tackle the global shortfall in radiotherapy services and the crisis of access to this highly effective treatment,” Dr Atun said.

With that in mind, he and his colleagues called for the following 6 targets to be met.

By 2020:

• 80% of countries to have comprehensive cancer plans that include radiotherapy.
• Each LMIC to create 1 new center for treatment and training.
• 80% of LMICs to include radiotherapy services in their universal health coverage plans.

By 2025:

• A 25% increase in radiotherapy treatment capacity.
• LMICs to train 7500 radiation oncologists, 20,000 radiotherapy radiographers, and 6000 medical physicists.
• $46 billion of upfront investment to be raised to establish radiotherapy infrastructure and training in LMICs (with help from international banks and the private sector).

“The evidence outlined in the [report] reinforces the case for investing in radiotherapy as an essential component of cancer control,” said Mary Gospodarowicz, MD, co-chair of the UICC Global Task Force on Radiotherapy for Cancer Control.

“The building of radiotherapy capacity will require large initial investment. However, the treatment is more cost-effective than chemotherapy and surgery for treating cancer, and the health and economic benefits will be realized in just 10 to 15 years.”

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

VIENNA—Millions of people throughout the world are dying from potentially treatable cancers because of a chronic underinvestment in radiotherapy resources, according to a new report.

The report suggests that expanding access to radiotherapy services will require a sizeable investment upfront, but that investment could bring economic benefits of up to $365 billion in developing countries over the next 20 years.

The report was published in The Lancet Oncology and presented at the 2015 European Cancer Congress.

The report estimates that 204 million fractions of radiotherapy will be needed to treat the 12 million cancer patients worldwide who could benefit from treatment in 2035.

But the cost per fraction is highly cost-effective and low compared to the price of many new cancer drugs, according to the report’s authors.

They estimate that full access to radiotherapy could be achieved for all patients in need in low-and middle income countries (LMIC) by 2035 for $97 billion, with potential health benefits of 27 million life-years saved and economic benefits ranging from $278 billion to $365 billion over the next 20 years.

“There is a widespread misconception that the costs of providing radiotherapy put it beyond the reach of all but the richest countries, [but] nothing could be further from the truth,” said Rifat Atun, MBBS, of Harvard University in Boston, Massachusetts.

“Our work . . .  clearly shows that not only can this essential service be deployed safely and high quality treatment delivered in low- and middle-income countries, but that scale-up of radiotherapy capacity is a feasible and highly cost-effective investment.”

The report provides details on access to radiotherapy services across the world, on a country-by-country basis. The authors calculated the costs and benefits of meeting the worldwide shortfall in resources and bridging the gap in access to effective treatment.

Estimates suggest that, at present, about 40% to 60% of cancer patients worldwide have access to radiotherapy. Even in high-income countries like Canada, Australia, and the UK, numbers of radiotherapy facilities, equipment, and trained staff are inadequate.

Access is worst in low-income countries, where as many as 9 out of 10 people cannot access radiotherapy. The problem of access is especially acute in Africa. In most African countries, radiotherapy is virtually non-existent. Forty countries have no radiotherapy facilities at all.

“The time has come to agree and implement immediate actions to tackle the global shortfall in radiotherapy services and the crisis of access to this highly effective treatment,” Dr Atun said.

With that in mind, he and his colleagues called for the following 6 targets to be met.

By 2020:

• 80% of countries to have comprehensive cancer plans that include radiotherapy.
• Each LMIC to create 1 new center for treatment and training.
• 80% of LMICs to include radiotherapy services in their universal health coverage plans.

By 2025:

• A 25% increase in radiotherapy treatment capacity.
• LMICs to train 7500 radiation oncologists, 20,000 radiotherapy radiographers, and 6000 medical physicists.
• $46 billion of upfront investment to be raised to establish radiotherapy infrastructure and training in LMICs (with help from international banks and the private sector).

“The evidence outlined in the [report] reinforces the case for investing in radiotherapy as an essential component of cancer control,” said Mary Gospodarowicz, MD, co-chair of the UICC Global Task Force on Radiotherapy for Cancer Control.

“The building of radiotherapy capacity will require large initial investment. However, the treatment is more cost-effective than chemotherapy and surgery for treating cancer, and the health and economic benefits will be realized in just 10 to 15 years.”

Patient undergoing CT scan

Photo by Angela Mary Butler

Clinicians should stratify patients with suspected acute pulmonary embolism (PE) to ensure use of the appropriate diagnostic strategy, according to guidelines from the American College of Physicians (ACP).

The ACP’s guidelines, published in Annals of Internal Medicine, are designed to help clinicians identify patients who should undergo diagnostic testing for PE—D-dimer and imaging—and those who should not.

“The use of computed tomography (CT) for the evaluation of patients with suspected pulmonary embolism is increasing, despite no evidence that this increased use has led to improved patient outcomes, while exposing patients to unnecessary risks and expense,” said ACP President Wayne J. Riley, MD.

“ACP’s advice is designed to help physicians identify patients for whom a PE is so unlikely that they need no further testing, for whom plasma D-dimer testing can provide additional risk stratification, and for whom imaging is indicated because of their high risk and clinical presentation.”

The guidelines say the first step for clinicians evaluating patients with suspected acute PE is to use a validated clinical prediction rule to estimate the patients’ pre-test probability of PE. The Wells and Geneva rules have been validated and are considered equally accurate in predicting the probability of PE.

In patients who have a low pre-test probability of PE, clinicians should apply the Pulmonary Embolism Rule-Out Criteria (PERC) rule. Clinicians should not obtain D-dimer tests or imaging studies in patients with a low pre-test probability of PE and who meet all 8 PERC.

Patients who have an intermediate pre-test probability of PE or patients with low pre-test probability of PE who do not meet all PERC should have a high sensitivity D-dimer test as the initial step in diagnosis.

Clinicians should not use imaging as the initial test in patients who have a low or intermediate pre-test probability of PE.

Since normal D-dimer levels increase with age, clinicians should use age-adjusted D-dimer thresholds (age times 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted.

Clinicians should not use imaging in low- or intermediate-risk patients with a D-dimer below the age-adjusted cutoff.

“While highly sensitive, plasma D-dimer testing is nonspecific, and false-positives can lead to unnecessary imaging,” said guideline author Ali S. Raja, MD, of Massachusetts General Hospital in Boston.

“The use of an age-adjusted threshold resulted in maintenance of sensitivities with improved specificities in all age groups.”

Patients with high pre-test probability of PE should undergo imaging with CT pulmonary angiography. Clinicians should reserve V/Q scans for patients who have a contraindication for CT pulmonary angiography or if CT pulmonary angiography is not available.

Clinicians should avoid obtaining a D-dimer measurement in patients with a high pre-test probability of PE.

Patient undergoing CT scan

Photo by Angela Mary Butler

Clinicians should stratify patients with suspected acute pulmonary embolism (PE) to ensure use of the appropriate diagnostic strategy, according to guidelines from the American College of Physicians (ACP).

The ACP’s guidelines, published in Annals of Internal Medicine, are designed to help clinicians identify patients who should undergo diagnostic testing for PE—D-dimer and imaging—and those who should not.

“The use of computed tomography (CT) for the evaluation of patients with suspected pulmonary embolism is increasing, despite no evidence that this increased use has led to improved patient outcomes, while exposing patients to unnecessary risks and expense,” said ACP President Wayne J. Riley, MD.

“ACP’s advice is designed to help physicians identify patients for whom a PE is so unlikely that they need no further testing, for whom plasma D-dimer testing can provide additional risk stratification, and for whom imaging is indicated because of their high risk and clinical presentation.”

The guidelines say the first step for clinicians evaluating patients with suspected acute PE is to use a validated clinical prediction rule to estimate the patients’ pre-test probability of PE. The Wells and Geneva rules have been validated and are considered equally accurate in predicting the probability of PE.

In patients who have a low pre-test probability of PE, clinicians should apply the Pulmonary Embolism Rule-Out Criteria (PERC) rule. Clinicians should not obtain D-dimer tests or imaging studies in patients with a low pre-test probability of PE and who meet all 8 PERC.

Patients who have an intermediate pre-test probability of PE or patients with low pre-test probability of PE who do not meet all PERC should have a high sensitivity D-dimer test as the initial step in diagnosis.

Clinicians should not use imaging as the initial test in patients who have a low or intermediate pre-test probability of PE.

Since normal D-dimer levels increase with age, clinicians should use age-adjusted D-dimer thresholds (age times 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted.

Clinicians should not use imaging in low- or intermediate-risk patients with a D-dimer below the age-adjusted cutoff.

“While highly sensitive, plasma D-dimer testing is nonspecific, and false-positives can lead to unnecessary imaging,” said guideline author Ali S. Raja, MD, of Massachusetts General Hospital in Boston.

“The use of an age-adjusted threshold resulted in maintenance of sensitivities with improved specificities in all age groups.”

Patients with high pre-test probability of PE should undergo imaging with CT pulmonary angiography. Clinicians should reserve V/Q scans for patients who have a contraindication for CT pulmonary angiography or if CT pulmonary angiography is not available.

Clinicians should avoid obtaining a D-dimer measurement in patients with a high pre-test probability of PE.

Patient undergoing CT scan

Photo by Angela Mary Butler

Clinicians should stratify patients with suspected acute pulmonary embolism (PE) to ensure use of the appropriate diagnostic strategy, according to guidelines from the American College of Physicians (ACP).

The ACP’s guidelines, published in Annals of Internal Medicine, are designed to help clinicians identify patients who should undergo diagnostic testing for PE—D-dimer and imaging—and those who should not.

“The use of computed tomography (CT) for the evaluation of patients with suspected pulmonary embolism is increasing, despite no evidence that this increased use has led to improved patient outcomes, while exposing patients to unnecessary risks and expense,” said ACP President Wayne J. Riley, MD.

“ACP’s advice is designed to help physicians identify patients for whom a PE is so unlikely that they need no further testing, for whom plasma D-dimer testing can provide additional risk stratification, and for whom imaging is indicated because of their high risk and clinical presentation.”

The guidelines say the first step for clinicians evaluating patients with suspected acute PE is to use a validated clinical prediction rule to estimate the patients’ pre-test probability of PE. The Wells and Geneva rules have been validated and are considered equally accurate in predicting the probability of PE.

In patients who have a low pre-test probability of PE, clinicians should apply the Pulmonary Embolism Rule-Out Criteria (PERC) rule. Clinicians should not obtain D-dimer tests or imaging studies in patients with a low pre-test probability of PE and who meet all 8 PERC.

Patients who have an intermediate pre-test probability of PE or patients with low pre-test probability of PE who do not meet all PERC should have a high sensitivity D-dimer test as the initial step in diagnosis.

Clinicians should not use imaging as the initial test in patients who have a low or intermediate pre-test probability of PE.

Since normal D-dimer levels increase with age, clinicians should use age-adjusted D-dimer thresholds (age times 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted.

Clinicians should not use imaging in low- or intermediate-risk patients with a D-dimer below the age-adjusted cutoff.

“While highly sensitive, plasma D-dimer testing is nonspecific, and false-positives can lead to unnecessary imaging,” said guideline author Ali S. Raja, MD, of Massachusetts General Hospital in Boston.

“The use of an age-adjusted threshold resulted in maintenance of sensitivities with improved specificities in all age groups.”

Patients with high pre-test probability of PE should undergo imaging with CT pulmonary angiography. Clinicians should reserve V/Q scans for patients who have a contraindication for CT pulmonary angiography or if CT pulmonary angiography is not available.

Clinicians should avoid obtaining a D-dimer measurement in patients with a high pre-test probability of PE.

Doctor and patient

Photo by Logan Tuttle

VIENNA—Despite progress made in recent years, there are “major problems” in pediatric oncology care in Europe, according to a report from the European Society for Paediatric Oncology (SIOPE).

Cancer is still the first cause of death by disease in children age 1 and older in Europe, and more than 300,000 European citizens are pediatric cancer survivors.

These individuals have a higher risk of death at 5 years after diagnosis than that of the general population.

“This is a serious problem for patients, their families, and for health services, with major inequalities existing across Europe,” said SIOPE President Gilles Vassal, MD, PhD, of the Institut Gustave Roussy in Villejuif, France.

“Add to this the fact that 35% of such cancers normally occur before the child is 5 years old and that many pediatric cancers are difficult to treat, and you will understand why we thought it essential to try to tackle this problem in a practical way.”

The resulting report, “The SIOPE Strategic Plan: A European Cancer Plan for Children and Adolescents,” was recently presented at the 2015 European Cancer Congress.

Problem-solving

The report was drawn up after widespread consultation, including discussions with parents, patients, and survivors. It sets out existing problems and proposes solutions to tackle them.

Among these problems are poor access to new drugs for pediatric patients; lack of funding; disparities across Europe in access to treatment and, hence, survival; and the fact that pediatric oncology has been relatively isolated from the adult oncology community.

With the goal of fixing these problems, the report sets out a number of goals and lists the key factors that will be necessary in order to achieve them.

These include a commitment of all funding bodies to finance projects and structures of relevance to pediatric oncology; a strong partnership with patients, parents, and survivors, including better communication and dissemination of information; better collaboration with adult oncology; and transparent partnerships with industry.

Understanding biology

“One of the most important objectives focuses on increasing our knowledge of the biology of pediatric tumors,” said SIOPE President-Elect Martin Schrappe, MD, of the University of Kiel, Germany.

“Cancers in adults result from a multistep process, usually after exposure to external carcinogens such as tobacco, alcohol, and diet, and often progress over many years. Pediatric malignancies develop early in life and over a much shorter time period. This suggests that fewer and stronger events are required for them to progress. Compared with adult cancers, most of them show fewer genetic defects and have a lower genetic complexity.”

“Major progress has been made in understanding pediatric tumor biology, and this has led to the discovery of some unique cancer hallmarks. Now, we need to use modern, innovative technologies to further decipher the mechanisms of pediatric tumor development, progression, and relapse, and speed up its translation to the clinic.”

To do this effectively and fairly, according to the report, interactions need to be strengthened at several levels—between networks of basic research teams, between basic scientists and clinical researchers, and by increasing the involvement of patients and parents in the search for personalized treatments. SIOPE plans to monitor progress through research into outcomes.

Improving quality of life

Another important issue for SIOPE is improving the quality of life for survivors.

“We believe that, in 2020, there will be nearly half a million European pediatric cancer survivors, and many of them will have side effects that are severe enough to affect their daily lives,” Dr Schrappe said. “While the fact that so many survive is a cause for rejoicing, we have a duty to provide them with optimal long-term care so that the rest of their lives may be as normal as possible.”

“One way of doing this would be the creation of a ‘survivorship passport’ for each child and adolescent cured of a cancer. This would contain a history of their disease and treatment, together with relevant follow-up measures aimed at improving their quality of life and a database for storing the clinical data [that would] facilitate monitoring and research.”

Doctor and patient

Photo by Logan Tuttle

VIENNA—Despite progress made in recent years, there are “major problems” in pediatric oncology care in Europe, according to a report from the European Society for Paediatric Oncology (SIOPE).

Cancer is still the first cause of death by disease in children age 1 and older in Europe, and more than 300,000 European citizens are pediatric cancer survivors.

These individuals have a higher risk of death at 5 years after diagnosis than that of the general population.

“This is a serious problem for patients, their families, and for health services, with major inequalities existing across Europe,” said SIOPE President Gilles Vassal, MD, PhD, of the Institut Gustave Roussy in Villejuif, France.

“Add to this the fact that 35% of such cancers normally occur before the child is 5 years old and that many pediatric cancers are difficult to treat, and you will understand why we thought it essential to try to tackle this problem in a practical way.”

The resulting report, “The SIOPE Strategic Plan: A European Cancer Plan for Children and Adolescents,” was recently presented at the 2015 European Cancer Congress.

Problem-solving

The report was drawn up after widespread consultation, including discussions with parents, patients, and survivors. It sets out existing problems and proposes solutions to tackle them.

Among these problems are poor access to new drugs for pediatric patients; lack of funding; disparities across Europe in access to treatment and, hence, survival; and the fact that pediatric oncology has been relatively isolated from the adult oncology community.

With the goal of fixing these problems, the report sets out a number of goals and lists the key factors that will be necessary in order to achieve them.

These include a commitment of all funding bodies to finance projects and structures of relevance to pediatric oncology; a strong partnership with patients, parents, and survivors, including better communication and dissemination of information; better collaboration with adult oncology; and transparent partnerships with industry.

Understanding biology

“One of the most important objectives focuses on increasing our knowledge of the biology of pediatric tumors,” said SIOPE President-Elect Martin Schrappe, MD, of the University of Kiel, Germany.

“Cancers in adults result from a multistep process, usually after exposure to external carcinogens such as tobacco, alcohol, and diet, and often progress over many years. Pediatric malignancies develop early in life and over a much shorter time period. This suggests that fewer and stronger events are required for them to progress. Compared with adult cancers, most of them show fewer genetic defects and have a lower genetic complexity.”

“Major progress has been made in understanding pediatric tumor biology, and this has led to the discovery of some unique cancer hallmarks. Now, we need to use modern, innovative technologies to further decipher the mechanisms of pediatric tumor development, progression, and relapse, and speed up its translation to the clinic.”

To do this effectively and fairly, according to the report, interactions need to be strengthened at several levels—between networks of basic research teams, between basic scientists and clinical researchers, and by increasing the involvement of patients and parents in the search for personalized treatments. SIOPE plans to monitor progress through research into outcomes.

Improving quality of life

Another important issue for SIOPE is improving the quality of life for survivors.

“We believe that, in 2020, there will be nearly half a million European pediatric cancer survivors, and many of them will have side effects that are severe enough to affect their daily lives,” Dr Schrappe said. “While the fact that so many survive is a cause for rejoicing, we have a duty to provide them with optimal long-term care so that the rest of their lives may be as normal as possible.”

“One way of doing this would be the creation of a ‘survivorship passport’ for each child and adolescent cured of a cancer. This would contain a history of their disease and treatment, together with relevant follow-up measures aimed at improving their quality of life and a database for storing the clinical data [that would] facilitate monitoring and research.”

Doctor and patient

Photo by Logan Tuttle

VIENNA—Despite progress made in recent years, there are “major problems” in pediatric oncology care in Europe, according to a report from the European Society for Paediatric Oncology (SIOPE).

Cancer is still the first cause of death by disease in children age 1 and older in Europe, and more than 300,000 European citizens are pediatric cancer survivors.

These individuals have a higher risk of death at 5 years after diagnosis than that of the general population.

“This is a serious problem for patients, their families, and for health services, with major inequalities existing across Europe,” said SIOPE President Gilles Vassal, MD, PhD, of the Institut Gustave Roussy in Villejuif, France.

“Add to this the fact that 35% of such cancers normally occur before the child is 5 years old and that many pediatric cancers are difficult to treat, and you will understand why we thought it essential to try to tackle this problem in a practical way.”

The resulting report, “The SIOPE Strategic Plan: A European Cancer Plan for Children and Adolescents,” was recently presented at the 2015 European Cancer Congress.

Problem-solving

The report was drawn up after widespread consultation, including discussions with parents, patients, and survivors. It sets out existing problems and proposes solutions to tackle them.

Among these problems are poor access to new drugs for pediatric patients; lack of funding; disparities across Europe in access to treatment and, hence, survival; and the fact that pediatric oncology has been relatively isolated from the adult oncology community.

With the goal of fixing these problems, the report sets out a number of goals and lists the key factors that will be necessary in order to achieve them.

These include a commitment of all funding bodies to finance projects and structures of relevance to pediatric oncology; a strong partnership with patients, parents, and survivors, including better communication and dissemination of information; better collaboration with adult oncology; and transparent partnerships with industry.

Understanding biology

“One of the most important objectives focuses on increasing our knowledge of the biology of pediatric tumors,” said SIOPE President-Elect Martin Schrappe, MD, of the University of Kiel, Germany.

“Cancers in adults result from a multistep process, usually after exposure to external carcinogens such as tobacco, alcohol, and diet, and often progress over many years. Pediatric malignancies develop early in life and over a much shorter time period. This suggests that fewer and stronger events are required for them to progress. Compared with adult cancers, most of them show fewer genetic defects and have a lower genetic complexity.”

“Major progress has been made in understanding pediatric tumor biology, and this has led to the discovery of some unique cancer hallmarks. Now, we need to use modern, innovative technologies to further decipher the mechanisms of pediatric tumor development, progression, and relapse, and speed up its translation to the clinic.”

To do this effectively and fairly, according to the report, interactions need to be strengthened at several levels—between networks of basic research teams, between basic scientists and clinical researchers, and by increasing the involvement of patients and parents in the search for personalized treatments. SIOPE plans to monitor progress through research into outcomes.

Improving quality of life

Another important issue for SIOPE is improving the quality of life for survivors.

“We believe that, in 2020, there will be nearly half a million European pediatric cancer survivors, and many of them will have side effects that are severe enough to affect their daily lives,” Dr Schrappe said. “While the fact that so many survive is a cause for rejoicing, we have a duty to provide them with optimal long-term care so that the rest of their lives may be as normal as possible.”

“One way of doing this would be the creation of a ‘survivorship passport’ for each child and adolescent cured of a cancer. This would contain a history of their disease and treatment, together with relevant follow-up measures aimed at improving their quality of life and a database for storing the clinical data [that would] facilitate monitoring and research.”

Micrograph showing AML

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).

The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.

The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.

Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.

AML-001 trial

The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.

Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.

Patients were then randomized to receive either azacitidine (75 mg/m²/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).

Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).

One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.

Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.

Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively. 

Micrograph showing AML

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).

The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.

The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.

Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.

AML-001 trial

The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.

Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.

Patients were then randomized to receive either azacitidine (75 mg/m²/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).

Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).

One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.

Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.

Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively. 

Micrograph showing AML

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).

The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.

The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.

Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.

AML-001 trial

The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.

Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.

Patients were then randomized to receive either azacitidine (75 mg/m²/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).

Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).

One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.

Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.

Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively. 

Pregnant woman

Photo by Nina Matthews

VIENNA—Women who are pregnant when diagnosed with cancer should carry their child to term but start cancer treatment immediately, according to researchers.

A study of young children suggested that exposure to cancer treatment in utero did not have detrimental effects on a child’s mental development or heart function.

Premature delivery, on the other hand, was associated with delayed cognitive development.

“Our results show that fear of cancer treatment is no reason to terminate a pregnancy, that maternal treatment should not be delayed, and that chemotherapy can be given,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.

“The study also shows that children suffer more from prematurity than from chemotherapy, so avoiding prematurity is more important than avoiding chemotherapy.”

Dr Amant presented these findings at the 2015 European Cancer Congress. The study was also published in NEJM.

The study included 129 children born to mothers with cancer, matched with 129 children of the same gestational age who were born to mothers unaffected by cancer.

The most common malignancies were breast (n=69) and hematologic cancers. This included acute myeloid leukemia (n=4), acute lymphoblastic leukemia (n=1), chronic myeloid leukemia (n=1), Hodgkin lymphoma (n=8), and non-Hodgkin lymphoma (n=6).

The researchers assessed the children’s general health and mental development when they were 18 months and 3 years old. At the age of 3, 47 of the children also had their heart function checked with electrocardiograms and echocardiography.

Ninety-six children (74.4%) were exposed to chemotherapy (alone or in combination with other treatment) before birth, 11 children (8.5%) were exposed to radiotherapy (alone or in combination), 13 (10.1%) were exposed to surgery alone, and 2 (1.6%) were exposed to drugs other than chemotherapeutic agents. Fourteen (10.9%) mothers did not receive cancer treatment during pregnancy.

Mental development

“Compared to the control group of children, we found no significant differences in mental development among children exposed to chemotherapy, radiotherapy, surgery alone, or no treatment,” Dr Amant said. “Nor was the number of chemotherapy cycles during pregnancy, which ranged from 1 to 10, related to the outcome of the children.”

To measure cognitive development, the researchers used the Bayley Scales of Infant Development. The median score was 101 (range, 56-145) in children exposed to cancer treatment and 100 (range, 50-145) in unexposed children.

When compared to controls, there was no significant difference in Bayley II or III score for all children born to mothers with cancer (P=0.08), children exposed to any chemotherapy (P=0.43), children exposed to anthracyclines (P=0.43), children exposed to taxanes (P=0.57), children exposed to platinum derivatives (P=0.95), children exposed to radiotherapy (P=0.69), children exposed to surgery alone (P=0.13), and children whose mothers did not undergo treatment (P=0.08).

Premature birth

Conversely, Bayley scores tended to increase by an average of 2.9 points for every week in gestational age. This was after the researchers controlled for a child’s age, gender, country, ethnicity, and parental education level.

“Delayed development of mental processes appeared to be related to premature birth,” Dr Amant said.

Premature birth was more frequent among children born to mothers with cancer, regardless of whether or not they received prenatal treatment, than in the general population in the countries participating in this study (Belgium, The Netherlands, Italy, and the Czech Republic).

The children born to mothers with cancer had a median gestational age of 36 weeks, ranging from 27 to 41 weeks. Seventy-nine (61.2%) children were born preterm, compared to 7% to 8% in the general population.

“In most cases, they were born prematurely due to a medical decision to induce preterm so as to continue cancer treatment after the delivery,” Dr Amant said.

“In some cases, preterm delivery was spontaneous, and it is possible that cancer treatment plays a role in this. But we do not know what exactly triggers preterm delivery. It could be that chemotherapy induces preterm contractions or vaginal inflammation with preterm rupture of the membranes.”

Cardiac function

The researchers assessed cardiac function in 47 three-year-olds whose mothers had cancer and 47 control children.

There were no significant differences between the exposed and control children for most measures of cardiac function, such as heart rate, ejection fraction, fractional shortening, global longitudinal strain, and circumferential strain.

The only exceptions were diastolic blood pressure, which was higher among exposed children (P=0.001), and tissue Doppler imaging measurements of the basal segment of the interventricular septum. There were higher mean peak systolic and early diastolic velocities in the control group than the exposed group (P=0.003 for both comparisons).

The researchers noted, however, that the differences in tissue Doppler velocities were not present when comparing the control group and the 26 children who were exposed to anthracyclines.

Next steps

Last year, Dr Amant reported similarly favorable results in 54 children exposed to chemotherapy or radiation in utero. The new report is a continuation of this work.

“These latest results are, again, reassuring,” Dr Amant said. “But given that we have a larger group of children . . . , the current data are much more robust.”

However, he also pointed out that this study has some limitations.

“Our data include many types of chemotherapy, but we cannot guarantee that all types of chemotherapy are safe,” Dr Amant said. “We need to look at larger numbers of children and larger numbers exposed to each drug in order to be able to document the potential effects of individual drugs.”

“In addition, we cannot extrapolate to newer drugs, including targeted drugs. We need longer follow-up to see if there are any long-term toxic effects in cases where cisplatin was administered before birth.”

“For these reasons, we will continue to follow these children until the age of 18 years, and we will enlarge the group. This will allow us to document longer-term effects and to draw conclusions for specific drugs. In addition, we will investigate to what extent anticancer drugs are diluted in the body during pregnancy and also [examine] the psycho-emotional needs of mothers and their partners.”

Pregnant woman

Photo by Nina Matthews

VIENNA—Women who are pregnant when diagnosed with cancer should carry their child to term but start cancer treatment immediately, according to researchers.

A study of young children suggested that exposure to cancer treatment in utero did not have detrimental effects on a child’s mental development or heart function.

Premature delivery, on the other hand, was associated with delayed cognitive development.

“Our results show that fear of cancer treatment is no reason to terminate a pregnancy, that maternal treatment should not be delayed, and that chemotherapy can be given,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.

“The study also shows that children suffer more from prematurity than from chemotherapy, so avoiding prematurity is more important than avoiding chemotherapy.”

Dr Amant presented these findings at the 2015 European Cancer Congress. The study was also published in NEJM.

The study included 129 children born to mothers with cancer, matched with 129 children of the same gestational age who were born to mothers unaffected by cancer.

The most common malignancies were breast (n=69) and hematologic cancers. This included acute myeloid leukemia (n=4), acute lymphoblastic leukemia (n=1), chronic myeloid leukemia (n=1), Hodgkin lymphoma (n=8), and non-Hodgkin lymphoma (n=6).

The researchers assessed the children’s general health and mental development when they were 18 months and 3 years old. At the age of 3, 47 of the children also had their heart function checked with electrocardiograms and echocardiography.

Ninety-six children (74.4%) were exposed to chemotherapy (alone or in combination with other treatment) before birth, 11 children (8.5%) were exposed to radiotherapy (alone or in combination), 13 (10.1%) were exposed to surgery alone, and 2 (1.6%) were exposed to drugs other than chemotherapeutic agents. Fourteen (10.9%) mothers did not receive cancer treatment during pregnancy.

Mental development

“Compared to the control group of children, we found no significant differences in mental development among children exposed to chemotherapy, radiotherapy, surgery alone, or no treatment,” Dr Amant said. “Nor was the number of chemotherapy cycles during pregnancy, which ranged from 1 to 10, related to the outcome of the children.”

To measure cognitive development, the researchers used the Bayley Scales of Infant Development. The median score was 101 (range, 56-145) in children exposed to cancer treatment and 100 (range, 50-145) in unexposed children.

When compared to controls, there was no significant difference in Bayley II or III score for all children born to mothers with cancer (P=0.08), children exposed to any chemotherapy (P=0.43), children exposed to anthracyclines (P=0.43), children exposed to taxanes (P=0.57), children exposed to platinum derivatives (P=0.95), children exposed to radiotherapy (P=0.69), children exposed to surgery alone (P=0.13), and children whose mothers did not undergo treatment (P=0.08).

Premature birth

Conversely, Bayley scores tended to increase by an average of 2.9 points for every week in gestational age. This was after the researchers controlled for a child’s age, gender, country, ethnicity, and parental education level.

“Delayed development of mental processes appeared to be related to premature birth,” Dr Amant said.

Premature birth was more frequent among children born to mothers with cancer, regardless of whether or not they received prenatal treatment, than in the general population in the countries participating in this study (Belgium, The Netherlands, Italy, and the Czech Republic).

The children born to mothers with cancer had a median gestational age of 36 weeks, ranging from 27 to 41 weeks. Seventy-nine (61.2%) children were born preterm, compared to 7% to 8% in the general population.

“In most cases, they were born prematurely due to a medical decision to induce preterm so as to continue cancer treatment after the delivery,” Dr Amant said.

“In some cases, preterm delivery was spontaneous, and it is possible that cancer treatment plays a role in this. But we do not know what exactly triggers preterm delivery. It could be that chemotherapy induces preterm contractions or vaginal inflammation with preterm rupture of the membranes.”

Cardiac function

The researchers assessed cardiac function in 47 three-year-olds whose mothers had cancer and 47 control children.

There were no significant differences between the exposed and control children for most measures of cardiac function, such as heart rate, ejection fraction, fractional shortening, global longitudinal strain, and circumferential strain.

The only exceptions were diastolic blood pressure, which was higher among exposed children (P=0.001), and tissue Doppler imaging measurements of the basal segment of the interventricular septum. There were higher mean peak systolic and early diastolic velocities in the control group than the exposed group (P=0.003 for both comparisons).

The researchers noted, however, that the differences in tissue Doppler velocities were not present when comparing the control group and the 26 children who were exposed to anthracyclines.

Next steps

Last year, Dr Amant reported similarly favorable results in 54 children exposed to chemotherapy or radiation in utero. The new report is a continuation of this work.

“These latest results are, again, reassuring,” Dr Amant said. “But given that we have a larger group of children . . . , the current data are much more robust.”

However, he also pointed out that this study has some limitations.

“Our data include many types of chemotherapy, but we cannot guarantee that all types of chemotherapy are safe,” Dr Amant said. “We need to look at larger numbers of children and larger numbers exposed to each drug in order to be able to document the potential effects of individual drugs.”

“In addition, we cannot extrapolate to newer drugs, including targeted drugs. We need longer follow-up to see if there are any long-term toxic effects in cases where cisplatin was administered before birth.”

“For these reasons, we will continue to follow these children until the age of 18 years, and we will enlarge the group. This will allow us to document longer-term effects and to draw conclusions for specific drugs. In addition, we will investigate to what extent anticancer drugs are diluted in the body during pregnancy and also [examine] the psycho-emotional needs of mothers and their partners.”

Pregnant woman

Photo by Nina Matthews

VIENNA—Women who are pregnant when diagnosed with cancer should carry their child to term but start cancer treatment immediately, according to researchers.

A study of young children suggested that exposure to cancer treatment in utero did not have detrimental effects on a child’s mental development or heart function.

Premature delivery, on the other hand, was associated with delayed cognitive development.

“Our results show that fear of cancer treatment is no reason to terminate a pregnancy, that maternal treatment should not be delayed, and that chemotherapy can be given,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.

“The study also shows that children suffer more from prematurity than from chemotherapy, so avoiding prematurity is more important than avoiding chemotherapy.”

Dr Amant presented these findings at the 2015 European Cancer Congress. The study was also published in NEJM.

The study included 129 children born to mothers with cancer, matched with 129 children of the same gestational age who were born to mothers unaffected by cancer.

The most common malignancies were breast (n=69) and hematologic cancers. This included acute myeloid leukemia (n=4), acute lymphoblastic leukemia (n=1), chronic myeloid leukemia (n=1), Hodgkin lymphoma (n=8), and non-Hodgkin lymphoma (n=6).

The researchers assessed the children’s general health and mental development when they were 18 months and 3 years old. At the age of 3, 47 of the children also had their heart function checked with electrocardiograms and echocardiography.

Ninety-six children (74.4%) were exposed to chemotherapy (alone or in combination with other treatment) before birth, 11 children (8.5%) were exposed to radiotherapy (alone or in combination), 13 (10.1%) were exposed to surgery alone, and 2 (1.6%) were exposed to drugs other than chemotherapeutic agents. Fourteen (10.9%) mothers did not receive cancer treatment during pregnancy.

Mental development

“Compared to the control group of children, we found no significant differences in mental development among children exposed to chemotherapy, radiotherapy, surgery alone, or no treatment,” Dr Amant said. “Nor was the number of chemotherapy cycles during pregnancy, which ranged from 1 to 10, related to the outcome of the children.”

To measure cognitive development, the researchers used the Bayley Scales of Infant Development. The median score was 101 (range, 56-145) in children exposed to cancer treatment and 100 (range, 50-145) in unexposed children.

When compared to controls, there was no significant difference in Bayley II or III score for all children born to mothers with cancer (P=0.08), children exposed to any chemotherapy (P=0.43), children exposed to anthracyclines (P=0.43), children exposed to taxanes (P=0.57), children exposed to platinum derivatives (P=0.95), children exposed to radiotherapy (P=0.69), children exposed to surgery alone (P=0.13), and children whose mothers did not undergo treatment (P=0.08).

Premature birth

Conversely, Bayley scores tended to increase by an average of 2.9 points for every week in gestational age. This was after the researchers controlled for a child’s age, gender, country, ethnicity, and parental education level.

“Delayed development of mental processes appeared to be related to premature birth,” Dr Amant said.

Premature birth was more frequent among children born to mothers with cancer, regardless of whether or not they received prenatal treatment, than in the general population in the countries participating in this study (Belgium, The Netherlands, Italy, and the Czech Republic).

The children born to mothers with cancer had a median gestational age of 36 weeks, ranging from 27 to 41 weeks. Seventy-nine (61.2%) children were born preterm, compared to 7% to 8% in the general population.

“In most cases, they were born prematurely due to a medical decision to induce preterm so as to continue cancer treatment after the delivery,” Dr Amant said.

“In some cases, preterm delivery was spontaneous, and it is possible that cancer treatment plays a role in this. But we do not know what exactly triggers preterm delivery. It could be that chemotherapy induces preterm contractions or vaginal inflammation with preterm rupture of the membranes.”

Cardiac function

The researchers assessed cardiac function in 47 three-year-olds whose mothers had cancer and 47 control children.

There were no significant differences between the exposed and control children for most measures of cardiac function, such as heart rate, ejection fraction, fractional shortening, global longitudinal strain, and circumferential strain.

The only exceptions were diastolic blood pressure, which was higher among exposed children (P=0.001), and tissue Doppler imaging measurements of the basal segment of the interventricular septum. There were higher mean peak systolic and early diastolic velocities in the control group than the exposed group (P=0.003 for both comparisons).

The researchers noted, however, that the differences in tissue Doppler velocities were not present when comparing the control group and the 26 children who were exposed to anthracyclines.

Next steps

Last year, Dr Amant reported similarly favorable results in 54 children exposed to chemotherapy or radiation in utero. The new report is a continuation of this work.

“These latest results are, again, reassuring,” Dr Amant said. “But given that we have a larger group of children . . . , the current data are much more robust.”

However, he also pointed out that this study has some limitations.

“Our data include many types of chemotherapy, but we cannot guarantee that all types of chemotherapy are safe,” Dr Amant said. “We need to look at larger numbers of children and larger numbers exposed to each drug in order to be able to document the potential effects of individual drugs.”

“In addition, we cannot extrapolate to newer drugs, including targeted drugs. We need longer follow-up to see if there are any long-term toxic effects in cases where cisplatin was administered before birth.”

“For these reasons, we will continue to follow these children until the age of 18 years, and we will enlarge the group. This will allow us to document longer-term effects and to draw conclusions for specific drugs. In addition, we will investigate to what extent anticancer drugs are diluted in the body during pregnancy and also [examine] the psycho-emotional needs of mothers and their partners.”