Lymphoma & Plasma Cell Disorders

Background The rates of depression in adults with cancer have been reported as high as 38%-58%. How depression affects overall health care expenditures in individuals with cancer is an under-researched area.

Objective To estimate excess average total health care expenditures associated with depression in adults with cancer by comparing those with and without depression after controlling for demographic, socioeconomic, access to care, and other health status variables.

Methods Cross-sectional data on 4,766 adult survivors of cancer from 2006-2009 of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS), were used. The patients were older than 21 years. Cancer and depression were identified from the patients’ medical conditions files. Dependent variables consisted of total, inpatient, outpatient, emergency department, prescription drugs, and other expenditures. Ordinary least square (OLS) on logged dollars and generalized linear models with log-link function were performed. All analyses (SAS 9.3 and STATA12) accounted for the complex survey design of the MEPS.

Results Overall, 14% of individuals with cancer reported having depression. In those with cancer and depression, the average annual health care expenditures were $18,401 compared with $12,091 in those without depression. After adjusting for demographic, socioeconomic, access to care, and other health status variables, those with depression had about 31.7% greater total expenditures compared with those without depression. Total, outpatient, and prescription expenditures were higher in individuals with depression than in those without depression. Individuals with cancer and depression were significantly more likely to use emergency departments (adjusted odds ratio, 1.46) compared with their counterparts without depression.

Limitations Cancer patients who died during the reporting year were excluded. The financial burden of depression may have been underestimated because the costs of end-of-life care are high. The burden for each cancer type was not analyzed because of the small sample size.

Conclusion In adults with cancer, those with depression had higher health care utilization and expenditures compared with those without depression.

Funding/sponsorship One author partially supported by the National Institute of General Medical Sciences, U54GM104942.

Click on the PDF icon at the top of this introduction to read the full article.

Background The rates of depression in adults with cancer have been reported as high as 38%-58%. How depression affects overall health care expenditures in individuals with cancer is an under-researched area.

Objective To estimate excess average total health care expenditures associated with depression in adults with cancer by comparing those with and without depression after controlling for demographic, socioeconomic, access to care, and other health status variables.

Methods Cross-sectional data on 4,766 adult survivors of cancer from 2006-2009 of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS), were used. The patients were older than 21 years. Cancer and depression were identified from the patients’ medical conditions files. Dependent variables consisted of total, inpatient, outpatient, emergency department, prescription drugs, and other expenditures. Ordinary least square (OLS) on logged dollars and generalized linear models with log-link function were performed. All analyses (SAS 9.3 and STATA12) accounted for the complex survey design of the MEPS.

Results Overall, 14% of individuals with cancer reported having depression. In those with cancer and depression, the average annual health care expenditures were $18,401 compared with $12,091 in those without depression. After adjusting for demographic, socioeconomic, access to care, and other health status variables, those with depression had about 31.7% greater total expenditures compared with those without depression. Total, outpatient, and prescription expenditures were higher in individuals with depression than in those without depression. Individuals with cancer and depression were significantly more likely to use emergency departments (adjusted odds ratio, 1.46) compared with their counterparts without depression.

Limitations Cancer patients who died during the reporting year were excluded. The financial burden of depression may have been underestimated because the costs of end-of-life care are high. The burden for each cancer type was not analyzed because of the small sample size.

Conclusion In adults with cancer, those with depression had higher health care utilization and expenditures compared with those without depression.

Funding/sponsorship One author partially supported by the National Institute of General Medical Sciences, U54GM104942.

Click on the PDF icon at the top of this introduction to read the full article.

Background The rates of depression in adults with cancer have been reported as high as 38%-58%. How depression affects overall health care expenditures in individuals with cancer is an under-researched area.

Objective To estimate excess average total health care expenditures associated with depression in adults with cancer by comparing those with and without depression after controlling for demographic, socioeconomic, access to care, and other health status variables.

Methods Cross-sectional data on 4,766 adult survivors of cancer from 2006-2009 of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS), were used. The patients were older than 21 years. Cancer and depression were identified from the patients’ medical conditions files. Dependent variables consisted of total, inpatient, outpatient, emergency department, prescription drugs, and other expenditures. Ordinary least square (OLS) on logged dollars and generalized linear models with log-link function were performed. All analyses (SAS 9.3 and STATA12) accounted for the complex survey design of the MEPS.

Results Overall, 14% of individuals with cancer reported having depression. In those with cancer and depression, the average annual health care expenditures were $18,401 compared with $12,091 in those without depression. After adjusting for demographic, socioeconomic, access to care, and other health status variables, those with depression had about 31.7% greater total expenditures compared with those without depression. Total, outpatient, and prescription expenditures were higher in individuals with depression than in those without depression. Individuals with cancer and depression were significantly more likely to use emergency departments (adjusted odds ratio, 1.46) compared with their counterparts without depression.

Limitations Cancer patients who died during the reporting year were excluded. The financial burden of depression may have been underestimated because the costs of end-of-life care are high. The burden for each cancer type was not analyzed because of the small sample size.

Conclusion In adults with cancer, those with depression had higher health care utilization and expenditures compared with those without depression.

Funding/sponsorship One author partially supported by the National Institute of General Medical Sciences, U54GM104942.

Click on the PDF icon at the top of this introduction to read the full article.

Researcher in the lab

Photo by Darren Baker

A newly developed database may help physicians predict survival outcomes in patients with hematologic and solid tumor malignancies, according to a paper published in Nature Medicine.

The database, known as PRECOG, integrates gene expression patterns of 39 types of cancer from nearly 18,000 patients with data about how long those patients lived.

By combining these data, researchers were able to see broad patterns that correlate with survival. They also believe this information could help them pinpoint potential therapeutic targets for a range of cancers.

“We were able to identify key pathways that can dramatically stratify survival across diverse cancer types,” said Ash Alizadeh, MD, PhD, of Stanford University in California.

“The patterns were very striking, especially because few such examples are currently available for the use of genes or immune cells for cancer prognosis.”

In addition to identifying potentially useful gene expression patterns, the researchers used an analytical tool called CIBERSORT to determine the composition of leukocytes that flock to a tumor.

“We were able to infer which immune cells are present or absent in individual solid tumors, to estimate their prevalence, and to correlate that information with patient survival,” said Aaron Newman, PhD, of Stanford University.

“We found you can even broadly distinguish cancer types just based on what kind of immune cells have infiltrated the tumor.”

Compiling the data

Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.

“There are many more genes in a cell than there are patients with any one type of cancer, and this makes discovering the important genes for cancer outcomes a tough problem,” said Andrew Gentles, PhD, of Stanford University.

“Because it’s easy to find spurious associations that don’t hold up in follow-up studies, we combined information from a vast array of cancer types to better see meaningful correlations.”

The researchers first collected publicly available data on gene expression patterns of many types of cancers.

They then matched the gene expression profiles with clinical information about the patients, including their age, disease status, and how long they survived after diagnosis. Finally, the team combined the studies in a database.

“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” Dr Alizadeh said. “Then, we could ask what we could learn more broadly.”

Surprising findings

The researchers were surprised to find that prognostic genes were often shared among distinct cancer types, suggesting that similar biological programs impact survival across cancers.

They were able to identify the top 10 genes that seemed to confer adverse outcomes—FOXM1, BIRC5, TOP2A, TPX2, NME1, CCNB1, CEP55, TYMS, CENPF, and CDKN3—and the top 10 genes associated with more positive outcomes—KLRB1, ITM2B, CBX7, CD2, CREBL2, SATB1, NR3C1, TMEM66, KLRK1, and FUCA1.

Many of these genes are involved in aspects of cell division or are associated with distinct leukocytes that flood a tumor.

The researchers were also able to identify combinations of leukocytes that appear to be correlated with outcomes.

In particular, elevated numbers of plasma cells and certain types of T cells correlated with better patient survival rates across many different solid tumors. But a high proportion of granulocytes was associated with adverse outcomes.

The researchers hope that PRECOG and CIBERSORT will increase our understanding of cancer biology and aid the development of new therapies for cancer patients. The team is applying these tools to better predict which patients will respond to new and emerging anticancer therapies.

Dr Alizadeh said this is especially important given recent advances in the development of drugs that engage immune responses but work well only for a subset of cancer patients.

Researcher in the lab

Photo by Darren Baker

A newly developed database may help physicians predict survival outcomes in patients with hematologic and solid tumor malignancies, according to a paper published in Nature Medicine.

The database, known as PRECOG, integrates gene expression patterns of 39 types of cancer from nearly 18,000 patients with data about how long those patients lived.

By combining these data, researchers were able to see broad patterns that correlate with survival. They also believe this information could help them pinpoint potential therapeutic targets for a range of cancers.

“We were able to identify key pathways that can dramatically stratify survival across diverse cancer types,” said Ash Alizadeh, MD, PhD, of Stanford University in California.

“The patterns were very striking, especially because few such examples are currently available for the use of genes or immune cells for cancer prognosis.”

In addition to identifying potentially useful gene expression patterns, the researchers used an analytical tool called CIBERSORT to determine the composition of leukocytes that flock to a tumor.

“We were able to infer which immune cells are present or absent in individual solid tumors, to estimate their prevalence, and to correlate that information with patient survival,” said Aaron Newman, PhD, of Stanford University.

“We found you can even broadly distinguish cancer types just based on what kind of immune cells have infiltrated the tumor.”

Compiling the data

Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.

“There are many more genes in a cell than there are patients with any one type of cancer, and this makes discovering the important genes for cancer outcomes a tough problem,” said Andrew Gentles, PhD, of Stanford University.

“Because it’s easy to find spurious associations that don’t hold up in follow-up studies, we combined information from a vast array of cancer types to better see meaningful correlations.”

The researchers first collected publicly available data on gene expression patterns of many types of cancers.

They then matched the gene expression profiles with clinical information about the patients, including their age, disease status, and how long they survived after diagnosis. Finally, the team combined the studies in a database.

“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” Dr Alizadeh said. “Then, we could ask what we could learn more broadly.”

Surprising findings

The researchers were surprised to find that prognostic genes were often shared among distinct cancer types, suggesting that similar biological programs impact survival across cancers.

They were able to identify the top 10 genes that seemed to confer adverse outcomes—FOXM1, BIRC5, TOP2A, TPX2, NME1, CCNB1, CEP55, TYMS, CENPF, and CDKN3—and the top 10 genes associated with more positive outcomes—KLRB1, ITM2B, CBX7, CD2, CREBL2, SATB1, NR3C1, TMEM66, KLRK1, and FUCA1.

Many of these genes are involved in aspects of cell division or are associated with distinct leukocytes that flood a tumor.

The researchers were also able to identify combinations of leukocytes that appear to be correlated with outcomes.

In particular, elevated numbers of plasma cells and certain types of T cells correlated with better patient survival rates across many different solid tumors. But a high proportion of granulocytes was associated with adverse outcomes.

The researchers hope that PRECOG and CIBERSORT will increase our understanding of cancer biology and aid the development of new therapies for cancer patients. The team is applying these tools to better predict which patients will respond to new and emerging anticancer therapies.

Dr Alizadeh said this is especially important given recent advances in the development of drugs that engage immune responses but work well only for a subset of cancer patients.

Researcher in the lab

Photo by Darren Baker

A newly developed database may help physicians predict survival outcomes in patients with hematologic and solid tumor malignancies, according to a paper published in Nature Medicine.

The database, known as PRECOG, integrates gene expression patterns of 39 types of cancer from nearly 18,000 patients with data about how long those patients lived.

By combining these data, researchers were able to see broad patterns that correlate with survival. They also believe this information could help them pinpoint potential therapeutic targets for a range of cancers.

“We were able to identify key pathways that can dramatically stratify survival across diverse cancer types,” said Ash Alizadeh, MD, PhD, of Stanford University in California.

“The patterns were very striking, especially because few such examples are currently available for the use of genes or immune cells for cancer prognosis.”

In addition to identifying potentially useful gene expression patterns, the researchers used an analytical tool called CIBERSORT to determine the composition of leukocytes that flock to a tumor.

“We were able to infer which immune cells are present or absent in individual solid tumors, to estimate their prevalence, and to correlate that information with patient survival,” said Aaron Newman, PhD, of Stanford University.

“We found you can even broadly distinguish cancer types just based on what kind of immune cells have infiltrated the tumor.”

Compiling the data

Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.

“There are many more genes in a cell than there are patients with any one type of cancer, and this makes discovering the important genes for cancer outcomes a tough problem,” said Andrew Gentles, PhD, of Stanford University.

“Because it’s easy to find spurious associations that don’t hold up in follow-up studies, we combined information from a vast array of cancer types to better see meaningful correlations.”

The researchers first collected publicly available data on gene expression patterns of many types of cancers.

They then matched the gene expression profiles with clinical information about the patients, including their age, disease status, and how long they survived after diagnosis. Finally, the team combined the studies in a database.

“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” Dr Alizadeh said. “Then, we could ask what we could learn more broadly.”

Surprising findings

The researchers were surprised to find that prognostic genes were often shared among distinct cancer types, suggesting that similar biological programs impact survival across cancers.

They were able to identify the top 10 genes that seemed to confer adverse outcomes—FOXM1, BIRC5, TOP2A, TPX2, NME1, CCNB1, CEP55, TYMS, CENPF, and CDKN3—and the top 10 genes associated with more positive outcomes—KLRB1, ITM2B, CBX7, CD2, CREBL2, SATB1, NR3C1, TMEM66, KLRK1, and FUCA1.

Many of these genes are involved in aspects of cell division or are associated with distinct leukocytes that flood a tumor.

The researchers were also able to identify combinations of leukocytes that appear to be correlated with outcomes.

In particular, elevated numbers of plasma cells and certain types of T cells correlated with better patient survival rates across many different solid tumors. But a high proportion of granulocytes was associated with adverse outcomes.

The researchers hope that PRECOG and CIBERSORT will increase our understanding of cancer biology and aid the development of new therapies for cancer patients. The team is applying these tools to better predict which patients will respond to new and emerging anticancer therapies.

Dr Alizadeh said this is especially important given recent advances in the development of drugs that engage immune responses but work well only for a subset of cancer patients.

Micrograph showing DLBCL

Researchers say they have found evidence linking disrupted metabolism and diffuse large B-cell lymphoma (DLBCL).

“The link between metabolism and cancer has been proposed or inferred to exist for a long time, but what is more scarce is evidence for a direct connection—genetic mutations in metabolic enzymes,” said Ricardo C.T. Aguiar, MD, PhD, of the University of Texas Health Science Center at San Antonio.

“We have discovered a metabolic imbalance that is oncogenic or pro-cancer.”

Dr Aguiar and his colleagues described this discovery in Nature Communications.

The team found that the gene encoding the enzyme D2-hydroxyglutarate dehydrogenase (D2HGDH) is mutated in DLBCL.

The mutated lymphoma cell displays a deficiency of a metabolite called alpha-ketoglutarate (α-KG), which is needed in steady levels for cells to be healthy.

“When the levels of α-KG are abnormally low, another class of enzymes called dioxygenases don‘t function properly, resulting in a host of additional disturbances,” Dr Aguiar said.

He added that α-KG has been identified as a critical regulator of aging and stem cell maintenance. So the implications of his group’s findings are not limited to cancer biology.

Micrograph showing DLBCL

Researchers say they have found evidence linking disrupted metabolism and diffuse large B-cell lymphoma (DLBCL).

“The link between metabolism and cancer has been proposed or inferred to exist for a long time, but what is more scarce is evidence for a direct connection—genetic mutations in metabolic enzymes,” said Ricardo C.T. Aguiar, MD, PhD, of the University of Texas Health Science Center at San Antonio.

“We have discovered a metabolic imbalance that is oncogenic or pro-cancer.”

Dr Aguiar and his colleagues described this discovery in Nature Communications.

The team found that the gene encoding the enzyme D2-hydroxyglutarate dehydrogenase (D2HGDH) is mutated in DLBCL.

The mutated lymphoma cell displays a deficiency of a metabolite called alpha-ketoglutarate (α-KG), which is needed in steady levels for cells to be healthy.

“When the levels of α-KG are abnormally low, another class of enzymes called dioxygenases don‘t function properly, resulting in a host of additional disturbances,” Dr Aguiar said.

He added that α-KG has been identified as a critical regulator of aging and stem cell maintenance. So the implications of his group’s findings are not limited to cancer biology.

Micrograph showing DLBCL

Researchers say they have found evidence linking disrupted metabolism and diffuse large B-cell lymphoma (DLBCL).

“The link between metabolism and cancer has been proposed or inferred to exist for a long time, but what is more scarce is evidence for a direct connection—genetic mutations in metabolic enzymes,” said Ricardo C.T. Aguiar, MD, PhD, of the University of Texas Health Science Center at San Antonio.

“We have discovered a metabolic imbalance that is oncogenic or pro-cancer.”

Dr Aguiar and his colleagues described this discovery in Nature Communications.

The team found that the gene encoding the enzyme D2-hydroxyglutarate dehydrogenase (D2HGDH) is mutated in DLBCL.

The mutated lymphoma cell displays a deficiency of a metabolite called alpha-ketoglutarate (α-KG), which is needed in steady levels for cells to be healthy.

“When the levels of α-KG are abnormally low, another class of enzymes called dioxygenases don‘t function properly, resulting in a host of additional disturbances,” Dr Aguiar said.

He added that α-KG has been identified as a critical regulator of aging and stem cell maintenance. So the implications of his group’s findings are not limited to cancer biology.

Wyndham Wilson, MD, PhD

Photo by Larry Young

Responses to the BTK inhibitor ibrutinib differ according to a patient’s subtype of diffuse large B-cell lymphoma (DLBCL), results of a phase 1/2 trial suggest.

The study showed that patients with activated B-cell-like (ABC) DLBCL were more likely to respond to ibrutinib than patients with germinal center B-cell-like (GCB) DLBCL.

“This is the first clinical study to demonstrate the importance of precision medicine in lymphomas,” said Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

Dr Wilson and his colleagues described the trial in Nature Medicine. The research, which was sponsored by Pharmacyclics, Inc. (the company developing ibrutinib), was previously presented at EHA 2013.

The trial enrolled 80 patients with relapsed or refractory DLBCL. All patients received ibrutinib. Tumor responses occurred in 25% of patients. There were 8 complete responses and 12 partial responses.

After a median follow-up of 11.5 months, the median progression-free survival was 1.6 months, and the median overall survival was 6.4 months.

An analysis of outcomes by disease subtype showed that ibrutinib produced complete or partial responses in 37% (14/38) of patients with ABC DLBCL but only 5% (1/20) of patients with GCB DLBCL.

The researchers speculated that ABC tumors may produce abnormal B-cell receptor signals that promote the survival of cancer cells by activating BTK, which would account for the sensitivity of ABC tumors to ibrutinib.

Based on this study’s results, researchers are conducting an international phase 3 trial of standard chemotherapy with or without ibrutinib in patients with DLBCL, excluding the GCB subtype (NCT01855750).

This is the first time a phase 3 trial has been designed to selectively enroll patients with a particular molecular subtype of DLBCL. The study’s objective is to determine if the addition of ibrutinib to standard chemotherapy can increase the cure rate of patients with ABC DLBCL.

Wyndham Wilson, MD, PhD

Photo by Larry Young

Responses to the BTK inhibitor ibrutinib differ according to a patient’s subtype of diffuse large B-cell lymphoma (DLBCL), results of a phase 1/2 trial suggest.

The study showed that patients with activated B-cell-like (ABC) DLBCL were more likely to respond to ibrutinib than patients with germinal center B-cell-like (GCB) DLBCL.

“This is the first clinical study to demonstrate the importance of precision medicine in lymphomas,” said Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

Dr Wilson and his colleagues described the trial in Nature Medicine. The research, which was sponsored by Pharmacyclics, Inc. (the company developing ibrutinib), was previously presented at EHA 2013.

The trial enrolled 80 patients with relapsed or refractory DLBCL. All patients received ibrutinib. Tumor responses occurred in 25% of patients. There were 8 complete responses and 12 partial responses.

After a median follow-up of 11.5 months, the median progression-free survival was 1.6 months, and the median overall survival was 6.4 months.

An analysis of outcomes by disease subtype showed that ibrutinib produced complete or partial responses in 37% (14/38) of patients with ABC DLBCL but only 5% (1/20) of patients with GCB DLBCL.

The researchers speculated that ABC tumors may produce abnormal B-cell receptor signals that promote the survival of cancer cells by activating BTK, which would account for the sensitivity of ABC tumors to ibrutinib.

Based on this study’s results, researchers are conducting an international phase 3 trial of standard chemotherapy with or without ibrutinib in patients with DLBCL, excluding the GCB subtype (NCT01855750).

This is the first time a phase 3 trial has been designed to selectively enroll patients with a particular molecular subtype of DLBCL. The study’s objective is to determine if the addition of ibrutinib to standard chemotherapy can increase the cure rate of patients with ABC DLBCL.

Wyndham Wilson, MD, PhD

Photo by Larry Young

Responses to the BTK inhibitor ibrutinib differ according to a patient’s subtype of diffuse large B-cell lymphoma (DLBCL), results of a phase 1/2 trial suggest.

The study showed that patients with activated B-cell-like (ABC) DLBCL were more likely to respond to ibrutinib than patients with germinal center B-cell-like (GCB) DLBCL.

“This is the first clinical study to demonstrate the importance of precision medicine in lymphomas,” said Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

Dr Wilson and his colleagues described the trial in Nature Medicine. The research, which was sponsored by Pharmacyclics, Inc. (the company developing ibrutinib), was previously presented at EHA 2013.

The trial enrolled 80 patients with relapsed or refractory DLBCL. All patients received ibrutinib. Tumor responses occurred in 25% of patients. There were 8 complete responses and 12 partial responses.

After a median follow-up of 11.5 months, the median progression-free survival was 1.6 months, and the median overall survival was 6.4 months.

An analysis of outcomes by disease subtype showed that ibrutinib produced complete or partial responses in 37% (14/38) of patients with ABC DLBCL but only 5% (1/20) of patients with GCB DLBCL.

The researchers speculated that ABC tumors may produce abnormal B-cell receptor signals that promote the survival of cancer cells by activating BTK, which would account for the sensitivity of ABC tumors to ibrutinib.

Based on this study’s results, researchers are conducting an international phase 3 trial of standard chemotherapy with or without ibrutinib in patients with DLBCL, excluding the GCB subtype (NCT01855750).

This is the first time a phase 3 trial has been designed to selectively enroll patients with a particular molecular subtype of DLBCL. The study’s objective is to determine if the addition of ibrutinib to standard chemotherapy can increase the cure rate of patients with ABC DLBCL.

Patient receiving chemotherapy

Photo by Rhoda Baer

New research suggests the polyphenols resveratrol and quercetin could be used to augment treatment with the anthracycline doxorubicin.

Investigators found they could increase the bioavailability of resveratrol and quercetin using copolymers that make the compounds water soluble and allow for their injection into the blood stream.

The team then showed the compounds synergize with doxorubicin while also reducing cardiac toxicity.

Although doxorubicin has proven effective against lymphomas, leukemias, and other cancers, the drug can only be used for a limited time because it confers cardiotoxicity.

The co-administration of resveratrol and quercetin might allow for much more extensive use of doxorubicin, while at the same time improving its efficacy and demonstrating the polyphenols’ own anticancer properties, investigators said.

They described research supporting this idea in the Journal of Controlled Release.

“This has great potential to improve chemotherapeutic cancer treatment,” said Adam Alani, PhD, of Oregon State University in Portland.

“The co-administration of high levels of resveratrol and quercetin, in both in vitro and in vivo studies, shows that it significantly reduces the cardiac toxicity of [doxorubicin]. And these compounds have a synergistic effect that enhances the efficacy of the cancer drug, by sensitizing the cancer cells to the effects of the drug.”

Dr Alani said further research may demonstrate that these compounds can completely eliminate the cardiotoxicity of doxorubicin, as they scavenge the toxic free radicals produced by this drug.

It’s also possible, he said, that administration of these natural polyphenols could have value in cancer therapy by themselves or in combination with a wider range of other chemotherapeutic drugs.

Increasing bioavailability

Resveratrol is a natural compound found in foods such as grapes, red wine, green tea, berries, and dark chocolate. Quercetin reaches some of its highest natural levels in capers, some berries, and leafy greens.

When consumed via food or taken as supplements, these polyphenol compounds reach only a tiny fraction of the level that’s possible with direct injection. Such injection was not possible until Dr Alani and his colleagues adapted the use of polymeric micelles.

Specifically, the investigators combined resveratrol and quercetin in Pluronic F127 micelles (mRQ). Pluronics are triblock copolymers consisting of a polypropylene oxide chain flanked with 2 polyethylene oxide chains that can self-assemble into polymeric micelles. The micelles have hydrophobic cores that help solubilize compounds with poor aqueous solubility.

“There are several advantages with this system,” Dr Alani said. “We can finally reach clinical levels of these polyphenols in the body. We can load both the compounds at one time to help control the cardiotoxicity of the cancer drug, and we can help the polyphenols accumulate in cancer cells where they have their own anticancer properties.”

In combination with doxorubicin

The investigators prepared mRQ micelles that were capable of retaining 1.1 mg/mL of resveratrol and 1.42 mg/mL of quercetin. They then tested mRQ in combination with doxorubicin in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2).

The team found that a resveratrol-quercetin-doxorubicin ratio of 10:10:1 was synergistic in SKOV-3 cells and antagonistic in H9C2 cells.

mRQ did not interfere with doxorubicin’s caspase activity in SKOV-3 cells but significantly decreased the activity in H9C2 cells. Likewise, there were no changes in the generation of reactive oxygen species in SKOV-3 cells, but there was significant scavenging in H9C2 cells.

The investigators also administered doxorubicin, with or without mRQ, to healthy mice and found that mRQ “conferred full cardioprotection.”

Dr Alani noted that previous research suggested resveratrol and quercetin are safe when given at high concentrations, but additional research is needed.

Patient receiving chemotherapy

Photo by Rhoda Baer

New research suggests the polyphenols resveratrol and quercetin could be used to augment treatment with the anthracycline doxorubicin.

Investigators found they could increase the bioavailability of resveratrol and quercetin using copolymers that make the compounds water soluble and allow for their injection into the blood stream.

The team then showed the compounds synergize with doxorubicin while also reducing cardiac toxicity.

Although doxorubicin has proven effective against lymphomas, leukemias, and other cancers, the drug can only be used for a limited time because it confers cardiotoxicity.

The co-administration of resveratrol and quercetin might allow for much more extensive use of doxorubicin, while at the same time improving its efficacy and demonstrating the polyphenols’ own anticancer properties, investigators said.

They described research supporting this idea in the Journal of Controlled Release.

“This has great potential to improve chemotherapeutic cancer treatment,” said Adam Alani, PhD, of Oregon State University in Portland.

“The co-administration of high levels of resveratrol and quercetin, in both in vitro and in vivo studies, shows that it significantly reduces the cardiac toxicity of [doxorubicin]. And these compounds have a synergistic effect that enhances the efficacy of the cancer drug, by sensitizing the cancer cells to the effects of the drug.”

Dr Alani said further research may demonstrate that these compounds can completely eliminate the cardiotoxicity of doxorubicin, as they scavenge the toxic free radicals produced by this drug.

It’s also possible, he said, that administration of these natural polyphenols could have value in cancer therapy by themselves or in combination with a wider range of other chemotherapeutic drugs.

Increasing bioavailability

Resveratrol is a natural compound found in foods such as grapes, red wine, green tea, berries, and dark chocolate. Quercetin reaches some of its highest natural levels in capers, some berries, and leafy greens.

When consumed via food or taken as supplements, these polyphenol compounds reach only a tiny fraction of the level that’s possible with direct injection. Such injection was not possible until Dr Alani and his colleagues adapted the use of polymeric micelles.

Specifically, the investigators combined resveratrol and quercetin in Pluronic F127 micelles (mRQ). Pluronics are triblock copolymers consisting of a polypropylene oxide chain flanked with 2 polyethylene oxide chains that can self-assemble into polymeric micelles. The micelles have hydrophobic cores that help solubilize compounds with poor aqueous solubility.

“There are several advantages with this system,” Dr Alani said. “We can finally reach clinical levels of these polyphenols in the body. We can load both the compounds at one time to help control the cardiotoxicity of the cancer drug, and we can help the polyphenols accumulate in cancer cells where they have their own anticancer properties.”

In combination with doxorubicin

The investigators prepared mRQ micelles that were capable of retaining 1.1 mg/mL of resveratrol and 1.42 mg/mL of quercetin. They then tested mRQ in combination with doxorubicin in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2).

The team found that a resveratrol-quercetin-doxorubicin ratio of 10:10:1 was synergistic in SKOV-3 cells and antagonistic in H9C2 cells.

mRQ did not interfere with doxorubicin’s caspase activity in SKOV-3 cells but significantly decreased the activity in H9C2 cells. Likewise, there were no changes in the generation of reactive oxygen species in SKOV-3 cells, but there was significant scavenging in H9C2 cells.

The investigators also administered doxorubicin, with or without mRQ, to healthy mice and found that mRQ “conferred full cardioprotection.”

Dr Alani noted that previous research suggested resveratrol and quercetin are safe when given at high concentrations, but additional research is needed.

Patient receiving chemotherapy

Photo by Rhoda Baer

New research suggests the polyphenols resveratrol and quercetin could be used to augment treatment with the anthracycline doxorubicin.

Investigators found they could increase the bioavailability of resveratrol and quercetin using copolymers that make the compounds water soluble and allow for their injection into the blood stream.

The team then showed the compounds synergize with doxorubicin while also reducing cardiac toxicity.

Although doxorubicin has proven effective against lymphomas, leukemias, and other cancers, the drug can only be used for a limited time because it confers cardiotoxicity.

The co-administration of resveratrol and quercetin might allow for much more extensive use of doxorubicin, while at the same time improving its efficacy and demonstrating the polyphenols’ own anticancer properties, investigators said.

They described research supporting this idea in the Journal of Controlled Release.

“This has great potential to improve chemotherapeutic cancer treatment,” said Adam Alani, PhD, of Oregon State University in Portland.

“The co-administration of high levels of resveratrol and quercetin, in both in vitro and in vivo studies, shows that it significantly reduces the cardiac toxicity of [doxorubicin]. And these compounds have a synergistic effect that enhances the efficacy of the cancer drug, by sensitizing the cancer cells to the effects of the drug.”

Dr Alani said further research may demonstrate that these compounds can completely eliminate the cardiotoxicity of doxorubicin, as they scavenge the toxic free radicals produced by this drug.

It’s also possible, he said, that administration of these natural polyphenols could have value in cancer therapy by themselves or in combination with a wider range of other chemotherapeutic drugs.

Increasing bioavailability

Resveratrol is a natural compound found in foods such as grapes, red wine, green tea, berries, and dark chocolate. Quercetin reaches some of its highest natural levels in capers, some berries, and leafy greens.

When consumed via food or taken as supplements, these polyphenol compounds reach only a tiny fraction of the level that’s possible with direct injection. Such injection was not possible until Dr Alani and his colleagues adapted the use of polymeric micelles.

Specifically, the investigators combined resveratrol and quercetin in Pluronic F127 micelles (mRQ). Pluronics are triblock copolymers consisting of a polypropylene oxide chain flanked with 2 polyethylene oxide chains that can self-assemble into polymeric micelles. The micelles have hydrophobic cores that help solubilize compounds with poor aqueous solubility.

“There are several advantages with this system,” Dr Alani said. “We can finally reach clinical levels of these polyphenols in the body. We can load both the compounds at one time to help control the cardiotoxicity of the cancer drug, and we can help the polyphenols accumulate in cancer cells where they have their own anticancer properties.”

In combination with doxorubicin

The investigators prepared mRQ micelles that were capable of retaining 1.1 mg/mL of resveratrol and 1.42 mg/mL of quercetin. They then tested mRQ in combination with doxorubicin in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2).

The team found that a resveratrol-quercetin-doxorubicin ratio of 10:10:1 was synergistic in SKOV-3 cells and antagonistic in H9C2 cells.

mRQ did not interfere with doxorubicin’s caspase activity in SKOV-3 cells but significantly decreased the activity in H9C2 cells. Likewise, there were no changes in the generation of reactive oxygen species in SKOV-3 cells, but there was significant scavenging in H9C2 cells.

The investigators also administered doxorubicin, with or without mRQ, to healthy mice and found that mRQ “conferred full cardioprotection.”

Dr Alani noted that previous research suggested resveratrol and quercetin are safe when given at high concentrations, but additional research is needed.

 

 

Pregnant woman

Photo by Nina Matthews

 

Researchers have again found evidence to suggest that tests used to identify chromosomal fetal disorders can detect occult malignancies in pregnant women.

In a study made public last month, non-invasive prenatal tests (NIPTs) revealed 2 cases of lymphoma and a case of ovarian cancer in expectant mothers.

In the new study, researchers showed that positive NIPT results were due to leukemia, lymphoma, or solid tumors in 10 expectant mothers.

The research was published in JAMA and presented at the 19th International Conference on Prenatal Diagnosis and Therapy in Washington, DC. Funding for the study was provided by Illumina, and company employees were involved in the research.

“We did this study because noninvasive prenatal testing using sequencing of cell-free DNA in the mother’s plasma is the fastest-growing area of prenatal testing and, indeed, of genomic medicine,” said study author Diana W. Bianchi, MD, of Tufts Medical Center in Boston, Massachusetts.

“As the volume of tests has expanded, we’ve become increasingly aware of the so-called “false-positive” cases. [A]pproximately 0.2% of the time, there is a discrepancy between the results of the prenatal test—in which an aneuploidy is reported—and the result from the diagnostic fetal procedure, the amniocentesis or the chorionic villus sampling.”

“So we’re interested in the situation where the fetal chromosomes are normal, but the prenatal test shows that there’s an aneuploidy detected. We’re interested in the possible explanations for that discrepancy.”

To gain some insight, Dr Bianchi and her colleagues evaluated 125,426 samples from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening using Illumina’s verifi Prenatal Test.

In all, 3757 samples (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. These were reported to the ordering physician with recommendations for further evaluation.

“In a small minority of women, [subsequent tests analyzing only fetal DNA] showed that the fetal chromosomes were normal, and that disagreed with [results of the NIPT],” Dr Bianchi said. “We were examining whether cancer could explain the discrepancy between these two test results.”

The researchers found that 10 of the women with discordant test results were subsequently diagnosed with cancer. There were 3 cases of B-cell lymphoma and 1 case each of T-cell leukemia, Hodgkin lymphoma, unspecified adenocarcinoma, leiomyosarcoma, and neuroendocrine, colorectal, and anal carcinomas.

Dr Bianchi and her colleagues were able to obtain detailed clinical and sequencing data for 8 of these cases. In the other 2 cases (leiomyosarcoma and unspecified adenocarcinoma), the women were critically ill and were not approached about participating in the study.

The researchers found that maternal cancers most frequently occurred when the NIPT detected more than 1 aneuploidy. There were 7 known cancers among 39 cases of multiple aneuploidies by NIPT. In 1 case, blood was sampled after the patient completed treatment for colorectal cancer, and the abnormal pattern was no longer evident.

When the researchers examined additional genetic information for the women with cancer, they found unique patterns of nonspecific copy-number gains and losses across multiple chromosomes.

“[These women] had DNA imbalances all across the genome,” Dr Bianchi said. “The [NIPT] normally is only looking at DNA material from the chromosomes of clinical interest—chromosomes 13, 18, 21, X, and Y.”

“When we opened up their results to look at all of the chromosomes, there were multiple abnormalities in other places, such as chromosome 8, chromosome 6, etc. Each woman had a unique pattern that was abnormal in many places. This suggested that it was the tumor DNA that was being shed into her blood and was contributing to the abnormal pattern.”

Dr Bianchi stressed that the tumor DNA did not affect the babies. She said all were born healthy, although labor was induced early in one mother to facilitate her cancer treatment.

 

 

Pregnant woman

Photo by Nina Matthews

 

Researchers have again found evidence to suggest that tests used to identify chromosomal fetal disorders can detect occult malignancies in pregnant women.

In a study made public last month, non-invasive prenatal tests (NIPTs) revealed 2 cases of lymphoma and a case of ovarian cancer in expectant mothers.

In the new study, researchers showed that positive NIPT results were due to leukemia, lymphoma, or solid tumors in 10 expectant mothers.

The research was published in JAMA and presented at the 19th International Conference on Prenatal Diagnosis and Therapy in Washington, DC. Funding for the study was provided by Illumina, and company employees were involved in the research.

“We did this study because noninvasive prenatal testing using sequencing of cell-free DNA in the mother’s plasma is the fastest-growing area of prenatal testing and, indeed, of genomic medicine,” said study author Diana W. Bianchi, MD, of Tufts Medical Center in Boston, Massachusetts.

“As the volume of tests has expanded, we’ve become increasingly aware of the so-called “false-positive” cases. [A]pproximately 0.2% of the time, there is a discrepancy between the results of the prenatal test—in which an aneuploidy is reported—and the result from the diagnostic fetal procedure, the amniocentesis or the chorionic villus sampling.”

“So we’re interested in the situation where the fetal chromosomes are normal, but the prenatal test shows that there’s an aneuploidy detected. We’re interested in the possible explanations for that discrepancy.”

To gain some insight, Dr Bianchi and her colleagues evaluated 125,426 samples from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening using Illumina’s verifi Prenatal Test.

In all, 3757 samples (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. These were reported to the ordering physician with recommendations for further evaluation.

“In a small minority of women, [subsequent tests analyzing only fetal DNA] showed that the fetal chromosomes were normal, and that disagreed with [results of the NIPT],” Dr Bianchi said. “We were examining whether cancer could explain the discrepancy between these two test results.”

The researchers found that 10 of the women with discordant test results were subsequently diagnosed with cancer. There were 3 cases of B-cell lymphoma and 1 case each of T-cell leukemia, Hodgkin lymphoma, unspecified adenocarcinoma, leiomyosarcoma, and neuroendocrine, colorectal, and anal carcinomas.

Dr Bianchi and her colleagues were able to obtain detailed clinical and sequencing data for 8 of these cases. In the other 2 cases (leiomyosarcoma and unspecified adenocarcinoma), the women were critically ill and were not approached about participating in the study.

The researchers found that maternal cancers most frequently occurred when the NIPT detected more than 1 aneuploidy. There were 7 known cancers among 39 cases of multiple aneuploidies by NIPT. In 1 case, blood was sampled after the patient completed treatment for colorectal cancer, and the abnormal pattern was no longer evident.

When the researchers examined additional genetic information for the women with cancer, they found unique patterns of nonspecific copy-number gains and losses across multiple chromosomes.

“[These women] had DNA imbalances all across the genome,” Dr Bianchi said. “The [NIPT] normally is only looking at DNA material from the chromosomes of clinical interest—chromosomes 13, 18, 21, X, and Y.”

“When we opened up their results to look at all of the chromosomes, there were multiple abnormalities in other places, such as chromosome 8, chromosome 6, etc. Each woman had a unique pattern that was abnormal in many places. This suggested that it was the tumor DNA that was being shed into her blood and was contributing to the abnormal pattern.”

Dr Bianchi stressed that the tumor DNA did not affect the babies. She said all were born healthy, although labor was induced early in one mother to facilitate her cancer treatment.

 

 

Pregnant woman

Photo by Nina Matthews

 

Researchers have again found evidence to suggest that tests used to identify chromosomal fetal disorders can detect occult malignancies in pregnant women.

In a study made public last month, non-invasive prenatal tests (NIPTs) revealed 2 cases of lymphoma and a case of ovarian cancer in expectant mothers.

In the new study, researchers showed that positive NIPT results were due to leukemia, lymphoma, or solid tumors in 10 expectant mothers.

The research was published in JAMA and presented at the 19th International Conference on Prenatal Diagnosis and Therapy in Washington, DC. Funding for the study was provided by Illumina, and company employees were involved in the research.

“We did this study because noninvasive prenatal testing using sequencing of cell-free DNA in the mother’s plasma is the fastest-growing area of prenatal testing and, indeed, of genomic medicine,” said study author Diana W. Bianchi, MD, of Tufts Medical Center in Boston, Massachusetts.

“As the volume of tests has expanded, we’ve become increasingly aware of the so-called “false-positive” cases. [A]pproximately 0.2% of the time, there is a discrepancy between the results of the prenatal test—in which an aneuploidy is reported—and the result from the diagnostic fetal procedure, the amniocentesis or the chorionic villus sampling.”

“So we’re interested in the situation where the fetal chromosomes are normal, but the prenatal test shows that there’s an aneuploidy detected. We’re interested in the possible explanations for that discrepancy.”

To gain some insight, Dr Bianchi and her colleagues evaluated 125,426 samples from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening using Illumina’s verifi Prenatal Test.

In all, 3757 samples (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. These were reported to the ordering physician with recommendations for further evaluation.

“In a small minority of women, [subsequent tests analyzing only fetal DNA] showed that the fetal chromosomes were normal, and that disagreed with [results of the NIPT],” Dr Bianchi said. “We were examining whether cancer could explain the discrepancy between these two test results.”

The researchers found that 10 of the women with discordant test results were subsequently diagnosed with cancer. There were 3 cases of B-cell lymphoma and 1 case each of T-cell leukemia, Hodgkin lymphoma, unspecified adenocarcinoma, leiomyosarcoma, and neuroendocrine, colorectal, and anal carcinomas.

Dr Bianchi and her colleagues were able to obtain detailed clinical and sequencing data for 8 of these cases. In the other 2 cases (leiomyosarcoma and unspecified adenocarcinoma), the women were critically ill and were not approached about participating in the study.

The researchers found that maternal cancers most frequently occurred when the NIPT detected more than 1 aneuploidy. There were 7 known cancers among 39 cases of multiple aneuploidies by NIPT. In 1 case, blood was sampled after the patient completed treatment for colorectal cancer, and the abnormal pattern was no longer evident.

When the researchers examined additional genetic information for the women with cancer, they found unique patterns of nonspecific copy-number gains and losses across multiple chromosomes.

“[These women] had DNA imbalances all across the genome,” Dr Bianchi said. “The [NIPT] normally is only looking at DNA material from the chromosomes of clinical interest—chromosomes 13, 18, 21, X, and Y.”

“When we opened up their results to look at all of the chromosomes, there were multiple abnormalities in other places, such as chromosome 8, chromosome 6, etc. Each woman had a unique pattern that was abnormal in many places. This suggested that it was the tumor DNA that was being shed into her blood and was contributing to the abnormal pattern.”

Dr Bianchi stressed that the tumor DNA did not affect the babies. She said all were born healthy, although labor was induced early in one mother to facilitate her cancer treatment.

Nancy Baxter, MD, PhD

Photo courtesy of

St. Michael’s Hospital

Up to 20 years after they are declared cancer-free, young adult (YA) cancer survivors are still hospitalized more often than the general population, according to research published in the Journal of Clinical Oncology.

Overall, the cancer survivors, who were ages 20 to 44 at diagnosis, were hospitalized about 1.5 times as often as control subjects.

“Even when young adults survive cancer, the cancer still has an impact on their lives and their long-term health, and this age group still has a lot of life to live,” said study author Nancy Baxter, MD, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

To conduct this study, Dr Baxter and her colleagues examined data from the Ontario Cancer Registry spanning the period from 1992 to 1999.

This included 20,275 patients who had their first cancer diagnosis between the ages of 20 and 44 and had lived for 5 years cancer-free. The researchers compared hospitalizations among these patients to hospitalizations in 101,344 non-cancer controls.

During the study period, 34.3% of cancer survivors (n=6948) were admitted to the hospital. The adjusted relative rate (ARR) of hospitalizations in survivors compared to controls was 1.51.

There was a significant decrease in hospitalizations among cancer survivors from the first time point the researchers analyzed to the last time point (P<0.0001).

But hospitalizations were more common among cancer survivors regardless of the time point. The ARR was 1.67 at 5 to 8 years after cancer diagnosis and 1.22 at 18 to 20 years after diagnosis.

When the researchers looked at individual malignancies, they found that survivors of melanoma or testicular cancer did not have higher rates of hospitalization than the control population. The ARRs were 0.97 and 1.07, respectively.

However, the rate of hospitalization was at least twice as high as the control population for survivors of leukemia (ARR=2.23) and lymphoma (ARR=2.02), as well as gastrointestinal (ARR=2.49), urologic (ARR=2.20), colorectal (ARR=2.10), and brain cancers (ARR=2.04).

Dr Baxter said having a better understanding of healthcare utilization and late effects in the YA cancer population may help healthcare providers counsel YA survivors on their future quality of life, identify areas where preventative strategies could be employed, and highlight the need to consider treatments that are not associated with long-term health consequences.

Nancy Baxter, MD, PhD

Photo courtesy of

St. Michael’s Hospital

Up to 20 years after they are declared cancer-free, young adult (YA) cancer survivors are still hospitalized more often than the general population, according to research published in the Journal of Clinical Oncology.

Overall, the cancer survivors, who were ages 20 to 44 at diagnosis, were hospitalized about 1.5 times as often as control subjects.

“Even when young adults survive cancer, the cancer still has an impact on their lives and their long-term health, and this age group still has a lot of life to live,” said study author Nancy Baxter, MD, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

To conduct this study, Dr Baxter and her colleagues examined data from the Ontario Cancer Registry spanning the period from 1992 to 1999.

This included 20,275 patients who had their first cancer diagnosis between the ages of 20 and 44 and had lived for 5 years cancer-free. The researchers compared hospitalizations among these patients to hospitalizations in 101,344 non-cancer controls.

During the study period, 34.3% of cancer survivors (n=6948) were admitted to the hospital. The adjusted relative rate (ARR) of hospitalizations in survivors compared to controls was 1.51.

There was a significant decrease in hospitalizations among cancer survivors from the first time point the researchers analyzed to the last time point (P<0.0001).

But hospitalizations were more common among cancer survivors regardless of the time point. The ARR was 1.67 at 5 to 8 years after cancer diagnosis and 1.22 at 18 to 20 years after diagnosis.

When the researchers looked at individual malignancies, they found that survivors of melanoma or testicular cancer did not have higher rates of hospitalization than the control population. The ARRs were 0.97 and 1.07, respectively.

However, the rate of hospitalization was at least twice as high as the control population for survivors of leukemia (ARR=2.23) and lymphoma (ARR=2.02), as well as gastrointestinal (ARR=2.49), urologic (ARR=2.20), colorectal (ARR=2.10), and brain cancers (ARR=2.04).

Dr Baxter said having a better understanding of healthcare utilization and late effects in the YA cancer population may help healthcare providers counsel YA survivors on their future quality of life, identify areas where preventative strategies could be employed, and highlight the need to consider treatments that are not associated with long-term health consequences.

Nancy Baxter, MD, PhD

Photo courtesy of

St. Michael’s Hospital

Up to 20 years after they are declared cancer-free, young adult (YA) cancer survivors are still hospitalized more often than the general population, according to research published in the Journal of Clinical Oncology.

Overall, the cancer survivors, who were ages 20 to 44 at diagnosis, were hospitalized about 1.5 times as often as control subjects.

“Even when young adults survive cancer, the cancer still has an impact on their lives and their long-term health, and this age group still has a lot of life to live,” said study author Nancy Baxter, MD, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

To conduct this study, Dr Baxter and her colleagues examined data from the Ontario Cancer Registry spanning the period from 1992 to 1999.

This included 20,275 patients who had their first cancer diagnosis between the ages of 20 and 44 and had lived for 5 years cancer-free. The researchers compared hospitalizations among these patients to hospitalizations in 101,344 non-cancer controls.

During the study period, 34.3% of cancer survivors (n=6948) were admitted to the hospital. The adjusted relative rate (ARR) of hospitalizations in survivors compared to controls was 1.51.

There was a significant decrease in hospitalizations among cancer survivors from the first time point the researchers analyzed to the last time point (P<0.0001).

But hospitalizations were more common among cancer survivors regardless of the time point. The ARR was 1.67 at 5 to 8 years after cancer diagnosis and 1.22 at 18 to 20 years after diagnosis.

When the researchers looked at individual malignancies, they found that survivors of melanoma or testicular cancer did not have higher rates of hospitalization than the control population. The ARRs were 0.97 and 1.07, respectively.

However, the rate of hospitalization was at least twice as high as the control population for survivors of leukemia (ARR=2.23) and lymphoma (ARR=2.02), as well as gastrointestinal (ARR=2.49), urologic (ARR=2.20), colorectal (ARR=2.10), and brain cancers (ARR=2.04).

Dr Baxter said having a better understanding of healthcare utilization and late effects in the YA cancer population may help healthcare providers counsel YA survivors on their future quality of life, identify areas where preventative strategies could be employed, and highlight the need to consider treatments that are not associated with long-term health consequences.

Adult lymphoma survivors who were treated with autologous hematopoietic stem-cell transplantation had a greater than sixfold increased risk of left ventricular systolic dysfunction compared with controls, according to a study published online in the Journal of Clinical Oncology.

Among 274 adult survivors of Hodgkin or non-Hodgkin lymphoma, 16% had left ventricular systolic dysfunction (LVSD): 11% had overt heart failure (HF) and 5% had asymptomatic LVSD, defined as a left ventricular ejection fraction of less than 50%.Heart symptoms were significantly associated with exposure to doxorubicin at a cumulative dose of 300 mg/m² or more and with cardiac radiation therapy of more than 30 Gy. Recognizing these patient risk factors allows for more intensive follow-up with the goal of “identification and early treatment of asymptomatic LVSD [which] may prevent the development of HF,” wrote Dr. Klaus Murbraech of Oslo University Hospital and his colleagues (J. Clin. Oncol. 2015 July 13 [doi:10.1200/JCO.2015.60.8125]).

The investigators observed no association between lower-dose cardiac radiation therapy and LVSD. There was only a marginally significant association between the presence of two or more traditional cardiovascular disease risk factors and LVSD.

The cross-sectional multicenter cohort study is the first to assess the prevalence of LVSD, according to Dr. Murbraech and his colleagues. The study included adult survivors of Hodgkin or non-Hodgkin lymphoma, median age 56 years, who underwent autologous stem-cell transplants in Norway from 1987 to 2008. The median observation time was 13 years (range, 4-34 years). The control group consisted of initially healthy patients in an echocardiographic follow-up study. Controls were matched to patients based on age, sex, systolic blood pressure, and body mass index.

The study was supported by the South-Eastern Norway Regional Health Authority and Extrastiftelsen. Dr. Murbraech reported having no disclosures.

Adult lymphoma survivors who were treated with autologous hematopoietic stem-cell transplantation had a greater than sixfold increased risk of left ventricular systolic dysfunction compared with controls, according to a study published online in the Journal of Clinical Oncology.

Among 274 adult survivors of Hodgkin or non-Hodgkin lymphoma, 16% had left ventricular systolic dysfunction (LVSD): 11% had overt heart failure (HF) and 5% had asymptomatic LVSD, defined as a left ventricular ejection fraction of less than 50%.Heart symptoms were significantly associated with exposure to doxorubicin at a cumulative dose of 300 mg/m² or more and with cardiac radiation therapy of more than 30 Gy. Recognizing these patient risk factors allows for more intensive follow-up with the goal of “identification and early treatment of asymptomatic LVSD [which] may prevent the development of HF,” wrote Dr. Klaus Murbraech of Oslo University Hospital and his colleagues (J. Clin. Oncol. 2015 July 13 [doi:10.1200/JCO.2015.60.8125]).

The investigators observed no association between lower-dose cardiac radiation therapy and LVSD. There was only a marginally significant association between the presence of two or more traditional cardiovascular disease risk factors and LVSD.

The cross-sectional multicenter cohort study is the first to assess the prevalence of LVSD, according to Dr. Murbraech and his colleagues. The study included adult survivors of Hodgkin or non-Hodgkin lymphoma, median age 56 years, who underwent autologous stem-cell transplants in Norway from 1987 to 2008. The median observation time was 13 years (range, 4-34 years). The control group consisted of initially healthy patients in an echocardiographic follow-up study. Controls were matched to patients based on age, sex, systolic blood pressure, and body mass index.

The study was supported by the South-Eastern Norway Regional Health Authority and Extrastiftelsen. Dr. Murbraech reported having no disclosures.

Adult lymphoma survivors who were treated with autologous hematopoietic stem-cell transplantation had a greater than sixfold increased risk of left ventricular systolic dysfunction compared with controls, according to a study published online in the Journal of Clinical Oncology.

Among 274 adult survivors of Hodgkin or non-Hodgkin lymphoma, 16% had left ventricular systolic dysfunction (LVSD): 11% had overt heart failure (HF) and 5% had asymptomatic LVSD, defined as a left ventricular ejection fraction of less than 50%.Heart symptoms were significantly associated with exposure to doxorubicin at a cumulative dose of 300 mg/m² or more and with cardiac radiation therapy of more than 30 Gy. Recognizing these patient risk factors allows for more intensive follow-up with the goal of “identification and early treatment of asymptomatic LVSD [which] may prevent the development of HF,” wrote Dr. Klaus Murbraech of Oslo University Hospital and his colleagues (J. Clin. Oncol. 2015 July 13 [doi:10.1200/JCO.2015.60.8125]).

The investigators observed no association between lower-dose cardiac radiation therapy and LVSD. There was only a marginally significant association between the presence of two or more traditional cardiovascular disease risk factors and LVSD.

The cross-sectional multicenter cohort study is the first to assess the prevalence of LVSD, according to Dr. Murbraech and his colleagues. The study included adult survivors of Hodgkin or non-Hodgkin lymphoma, median age 56 years, who underwent autologous stem-cell transplants in Norway from 1987 to 2008. The median observation time was 13 years (range, 4-34 years). The control group consisted of initially healthy patients in an echocardiographic follow-up study. Controls were matched to patients based on age, sex, systolic blood pressure, and body mass index.

The study was supported by the South-Eastern Norway Regional Health Authority and Extrastiftelsen. Dr. Murbraech reported having no disclosures.

Red and white blood cells

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guideline on hematopoietic colony-stimulating factors (CSFs).

The guideline includes recommendations on the use of CSFs in the context of lymphoma, solid tumor malignancies, pediatric leukemia, and hematopoietic stem cell transplant.

There are no recommendations pertaining to adults with acute myeloid leukemia or myelodysplastic syndromes.

ASCO’s previous guideline on CSFs was issued in 2006. For the update, an ASCO expert panel conducted a formal systematic review of relevant articles from the medical literature published from October 2005 through September 2014.

Key recommendations from the resulting guideline are as follows.

Pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia.

For patients with lymphomas or solid tumors, primary prophylaxis with a CSF should be given during all cycles of chemotherapy in patients who have an approximately 20% or higher risk for febrile neutropenia on the basis of patient-, disease-, and treatment-related factors.

However, clinicians should also consider using chemotherapy regimens that do not require CSF administration but are as effective as regimens that do require a CSF.

Patients with lymphomas or solid tumors should receive secondary febrile neutropenia prophylaxis with a CSF if they experienced a neutropenic complication from a previous cycle of chemotherapy (for which they did not receive primary prophylaxis) when a reduced dose or treatment delay may compromise disease-free survival, overall survival, or treatment outcome.

However, the guideline also says that, in many clinical situations, dose reductions or delays may be a reasonable alternative.

CSFs should not be routinely used for patients with neutropenia who are afebrile or as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia.

Dose-dense regimens with CSF support should only be used within an appropriately designed clinical trial or if use of the regimen is supported by convincing efficacy data. The guideline says that, for non-Hodgkin lymphoma, data on the value of dose-dense regimens with CSF support are limited and conflicting.

In the context of transplant, CSFs may be used alone, after chemotherapy, or in combination with plerixafor to mobilize peripheral blood stem cells. To reduce the duration of severe neutropenia, CSFs should be administered after autologous stem cell transplant and may be administered after allogeneic stem cell transplant.

CSFs should be avoided in patients receiving concomitant chemotherapy and radiation, particularly involving the mediastinum. CSFs may be considered in patients receiving radiation alone if the clinician expects prolonged treatment delays due to neutropenia.

Patients who are exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, should promptly receive CSFs or pegylated granulocyte CSFs.

Clinicians should consider prophylactic CSF for patients with diffuse aggressive lymphoma who are 65 or older and are receiving curative chemotherapy (R-CHOP), particularly if they have comorbidities.

The guideline also says the use of CSFs in pediatric patients will almost always be guided by clinical protocols. But CSFs should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection.

For more details, see the complete guideline. ASCO said it encourages feedback on its guidelines from oncologists, practitioners, and patients through the ASCO Guidelines Wiki.

Red and white blood cells

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guideline on hematopoietic colony-stimulating factors (CSFs).

The guideline includes recommendations on the use of CSFs in the context of lymphoma, solid tumor malignancies, pediatric leukemia, and hematopoietic stem cell transplant.

There are no recommendations pertaining to adults with acute myeloid leukemia or myelodysplastic syndromes.

ASCO’s previous guideline on CSFs was issued in 2006. For the update, an ASCO expert panel conducted a formal systematic review of relevant articles from the medical literature published from October 2005 through September 2014.

Key recommendations from the resulting guideline are as follows.

Pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia.

For patients with lymphomas or solid tumors, primary prophylaxis with a CSF should be given during all cycles of chemotherapy in patients who have an approximately 20% or higher risk for febrile neutropenia on the basis of patient-, disease-, and treatment-related factors.

However, clinicians should also consider using chemotherapy regimens that do not require CSF administration but are as effective as regimens that do require a CSF.

Patients with lymphomas or solid tumors should receive secondary febrile neutropenia prophylaxis with a CSF if they experienced a neutropenic complication from a previous cycle of chemotherapy (for which they did not receive primary prophylaxis) when a reduced dose or treatment delay may compromise disease-free survival, overall survival, or treatment outcome.

However, the guideline also says that, in many clinical situations, dose reductions or delays may be a reasonable alternative.

CSFs should not be routinely used for patients with neutropenia who are afebrile or as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia.

Dose-dense regimens with CSF support should only be used within an appropriately designed clinical trial or if use of the regimen is supported by convincing efficacy data. The guideline says that, for non-Hodgkin lymphoma, data on the value of dose-dense regimens with CSF support are limited and conflicting.

In the context of transplant, CSFs may be used alone, after chemotherapy, or in combination with plerixafor to mobilize peripheral blood stem cells. To reduce the duration of severe neutropenia, CSFs should be administered after autologous stem cell transplant and may be administered after allogeneic stem cell transplant.

CSFs should be avoided in patients receiving concomitant chemotherapy and radiation, particularly involving the mediastinum. CSFs may be considered in patients receiving radiation alone if the clinician expects prolonged treatment delays due to neutropenia.

Patients who are exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, should promptly receive CSFs or pegylated granulocyte CSFs.

Clinicians should consider prophylactic CSF for patients with diffuse aggressive lymphoma who are 65 or older and are receiving curative chemotherapy (R-CHOP), particularly if they have comorbidities.

The guideline also says the use of CSFs in pediatric patients will almost always be guided by clinical protocols. But CSFs should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection.

For more details, see the complete guideline. ASCO said it encourages feedback on its guidelines from oncologists, practitioners, and patients through the ASCO Guidelines Wiki.

Red and white blood cells

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guideline on hematopoietic colony-stimulating factors (CSFs).

The guideline includes recommendations on the use of CSFs in the context of lymphoma, solid tumor malignancies, pediatric leukemia, and hematopoietic stem cell transplant.

There are no recommendations pertaining to adults with acute myeloid leukemia or myelodysplastic syndromes.

ASCO’s previous guideline on CSFs was issued in 2006. For the update, an ASCO expert panel conducted a formal systematic review of relevant articles from the medical literature published from October 2005 through September 2014.

Key recommendations from the resulting guideline are as follows.

Pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia.

For patients with lymphomas or solid tumors, primary prophylaxis with a CSF should be given during all cycles of chemotherapy in patients who have an approximately 20% or higher risk for febrile neutropenia on the basis of patient-, disease-, and treatment-related factors.

However, clinicians should also consider using chemotherapy regimens that do not require CSF administration but are as effective as regimens that do require a CSF.

Patients with lymphomas or solid tumors should receive secondary febrile neutropenia prophylaxis with a CSF if they experienced a neutropenic complication from a previous cycle of chemotherapy (for which they did not receive primary prophylaxis) when a reduced dose or treatment delay may compromise disease-free survival, overall survival, or treatment outcome.

However, the guideline also says that, in many clinical situations, dose reductions or delays may be a reasonable alternative.

CSFs should not be routinely used for patients with neutropenia who are afebrile or as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia.

Dose-dense regimens with CSF support should only be used within an appropriately designed clinical trial or if use of the regimen is supported by convincing efficacy data. The guideline says that, for non-Hodgkin lymphoma, data on the value of dose-dense regimens with CSF support are limited and conflicting.

In the context of transplant, CSFs may be used alone, after chemotherapy, or in combination with plerixafor to mobilize peripheral blood stem cells. To reduce the duration of severe neutropenia, CSFs should be administered after autologous stem cell transplant and may be administered after allogeneic stem cell transplant.

CSFs should be avoided in patients receiving concomitant chemotherapy and radiation, particularly involving the mediastinum. CSFs may be considered in patients receiving radiation alone if the clinician expects prolonged treatment delays due to neutropenia.

Patients who are exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, should promptly receive CSFs or pegylated granulocyte CSFs.

Clinicians should consider prophylactic CSF for patients with diffuse aggressive lymphoma who are 65 or older and are receiving curative chemotherapy (R-CHOP), particularly if they have comorbidities.

The guideline also says the use of CSFs in pediatric patients will almost always be guided by clinical protocols. But CSFs should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection.

For more details, see the complete guideline. ASCO said it encourages feedback on its guidelines from oncologists, practitioners, and patients through the ASCO Guidelines Wiki.