Leukemia, Myelodysplasia, Transplantation

Blood smear showing MDS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending lenalidomide (Revlimid) as an option for treating myelodysplastic syndromes (MDS) characterized by 5q deletion.

Lenalidomide is approved in the European Union to treat transfusion-dependent anemia caused by low- or intermediate-1 risk MDS characterized by 5q deletion when other therapeutic options are insufficient or inadequate.

However, the main treatment option for this patient population in the UK is best supportive care, which involves regular red blood cell transfusions.

In earlier draft guidances, NICE did not support lenalidomide use in MDS patients with 5q deletion. Although data suggested the drug is effective for these patients, a NICE advisory committee was not convinced the drug provided a survival benefit.

But now, the committee has concluded that lenalidomide is a clinically effective treatment for these patients because it is associated with a statistically significant improvement in transfusion independence and health-related quality of life compared with placebo.

Furthermore, the committee said it is plausible that lenalidomide can indirectly improve overall survival by improving transfusion independence.

“The committee heard from clinical experts that lenalidomide is an effective therapy,” said Sir Andrew Dillon, NICE chief executive.

“Celgene–who market lenalidomide–worked with us to provide enough evidence to make it possible for us to recommend it for this group of people. Celgene provided a revised analysis and further information on their proposal for a reduction in the cost of the drug to the NHS [National Health Service].”

This patient access scheme involves the NHS paying for lenalidomide treatment for up to 26 monthly cycles. And Celgene will provide the drug free of charge for those people who receive more than 26 monthly cycles.

Lenalidomide is available in 21-day packs of 10 mg and 5 mg capsules at net prices of £3780 and £3570, respectively. The cost of a 28-day cycle of treatment with 10 mg of lenalidomide (excluding value-added tax) is £3780.

The committee noted that the incremental cost-effectiveness ratio for lenalidomide compared with best supportive care is uncertain because the proportion of people who might need treatment beyond 26 cycles is uncertain.

However, the committee accepted that a commitment from Celgene to publish data on the proportion of people receiving treatment beyond 26 cycles would provide reassurance that lenalidomide is a cost-effective use of NHS resources in MDS patients with 5q deletion.

NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.

Blood smear showing MDS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending lenalidomide (Revlimid) as an option for treating myelodysplastic syndromes (MDS) characterized by 5q deletion.

Lenalidomide is approved in the European Union to treat transfusion-dependent anemia caused by low- or intermediate-1 risk MDS characterized by 5q deletion when other therapeutic options are insufficient or inadequate.

However, the main treatment option for this patient population in the UK is best supportive care, which involves regular red blood cell transfusions.

In earlier draft guidances, NICE did not support lenalidomide use in MDS patients with 5q deletion. Although data suggested the drug is effective for these patients, a NICE advisory committee was not convinced the drug provided a survival benefit.

But now, the committee has concluded that lenalidomide is a clinically effective treatment for these patients because it is associated with a statistically significant improvement in transfusion independence and health-related quality of life compared with placebo.

Furthermore, the committee said it is plausible that lenalidomide can indirectly improve overall survival by improving transfusion independence.

“The committee heard from clinical experts that lenalidomide is an effective therapy,” said Sir Andrew Dillon, NICE chief executive.

“Celgene–who market lenalidomide–worked with us to provide enough evidence to make it possible for us to recommend it for this group of people. Celgene provided a revised analysis and further information on their proposal for a reduction in the cost of the drug to the NHS [National Health Service].”

This patient access scheme involves the NHS paying for lenalidomide treatment for up to 26 monthly cycles. And Celgene will provide the drug free of charge for those people who receive more than 26 monthly cycles.

Lenalidomide is available in 21-day packs of 10 mg and 5 mg capsules at net prices of £3780 and £3570, respectively. The cost of a 28-day cycle of treatment with 10 mg of lenalidomide (excluding value-added tax) is £3780.

The committee noted that the incremental cost-effectiveness ratio for lenalidomide compared with best supportive care is uncertain because the proportion of people who might need treatment beyond 26 cycles is uncertain.

However, the committee accepted that a commitment from Celgene to publish data on the proportion of people receiving treatment beyond 26 cycles would provide reassurance that lenalidomide is a cost-effective use of NHS resources in MDS patients with 5q deletion.

NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.

Blood smear showing MDS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending lenalidomide (Revlimid) as an option for treating myelodysplastic syndromes (MDS) characterized by 5q deletion.

Lenalidomide is approved in the European Union to treat transfusion-dependent anemia caused by low- or intermediate-1 risk MDS characterized by 5q deletion when other therapeutic options are insufficient or inadequate.

However, the main treatment option for this patient population in the UK is best supportive care, which involves regular red blood cell transfusions.

In earlier draft guidances, NICE did not support lenalidomide use in MDS patients with 5q deletion. Although data suggested the drug is effective for these patients, a NICE advisory committee was not convinced the drug provided a survival benefit.

But now, the committee has concluded that lenalidomide is a clinically effective treatment for these patients because it is associated with a statistically significant improvement in transfusion independence and health-related quality of life compared with placebo.

Furthermore, the committee said it is plausible that lenalidomide can indirectly improve overall survival by improving transfusion independence.

“The committee heard from clinical experts that lenalidomide is an effective therapy,” said Sir Andrew Dillon, NICE chief executive.

“Celgene–who market lenalidomide–worked with us to provide enough evidence to make it possible for us to recommend it for this group of people. Celgene provided a revised analysis and further information on their proposal for a reduction in the cost of the drug to the NHS [National Health Service].”

This patient access scheme involves the NHS paying for lenalidomide treatment for up to 26 monthly cycles. And Celgene will provide the drug free of charge for those people who receive more than 26 monthly cycles.

Lenalidomide is available in 21-day packs of 10 mg and 5 mg capsules at net prices of £3780 and £3570, respectively. The cost of a 28-day cycle of treatment with 10 mg of lenalidomide (excluding value-added tax) is £3780.

The committee noted that the incremental cost-effectiveness ratio for lenalidomide compared with best supportive care is uncertain because the proportion of people who might need treatment beyond 26 cycles is uncertain.

However, the committee accepted that a commitment from Celgene to publish data on the proportion of people receiving treatment beyond 26 cycles would provide reassurance that lenalidomide is a cost-effective use of NHS resources in MDS patients with 5q deletion.

NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.

An NK cell in action

Credit: Bjorn Onfelt/Dan Davis

In vitro experiments suggest a patient’s own natural killer (NK) cells can be expanded and modified to fight acute lymphoblastic leukemia (ALL).

Researchers successfully expanded CD56+ cells isolated from the bone marrow and peripheral blood of ALL patients.

And these cells exhibited cytotoxicity against the patients’ own ALL cells. The effect was enhanced by the addition of IL-15 and a monoclonal antibody (mAb) targeting BAFF-R.

Hisham Abdel-Azim, MD, of Children’s Hospital Los Angeles, and his colleagues reported these results in Leukemia.

The researchers first used flow cytometry to detect CD56+ cells in bone marrow and peripheral blood samples from ALL patients. The team discovered these cells were detectable at diagnosis, post-induction, and relapse.

To expand the cells, the researchers cocultured them with artificial antigen-presenting K562 clone 9.mbIL-21 cells. The expanded CD56+ cells demonstrated allogeneic cytotoxicity against ALL cells, even in the absence of antibody.

The addition of a mAb targeting BAFF-R enhanced CD56+ cells’ cytotoxicity against ALL cells. The activity of these CD56+ cells was comparable to that of NK cells derived from healthy patients.

The researchers also compared CD56+CD3- cells to CD56+CD3+ cells and found the CD3- cells exhibited increased levels of activation in antibody-mediated cellular cytotoxicity reactions. The CD56+CD3+ cells were not stimulated by BAFF-R mAbs.

The team then tested the NK cells’ autologous cytotoxicity. And, as in previous experiments, the CD56+ cells from ALL samples demonstrated nonantibody-dependent cytotoxicity and enhanced cytotoxicity in the presence of BAFF-R mAbs.

Finally, the researchers decided to investigate whether the addition of IL-2 or IL-15 could further stimulate CD56+ cells’ cytotoxicity. And while they found that both cytokines did the job, IL-15 proved more successful.

“These results are very promising, with potential as a part of first-line therapy and also as a treatment for eliminating any remaining cancer cells . . . following standard chemotherapy,” Dr Abdel-Azim said. “We anticipate additional preclinical testing and then a clinical trial to evaluate the therapy in children with leukemia.”

An NK cell in action

Credit: Bjorn Onfelt/Dan Davis

In vitro experiments suggest a patient’s own natural killer (NK) cells can be expanded and modified to fight acute lymphoblastic leukemia (ALL).

Researchers successfully expanded CD56+ cells isolated from the bone marrow and peripheral blood of ALL patients.

And these cells exhibited cytotoxicity against the patients’ own ALL cells. The effect was enhanced by the addition of IL-15 and a monoclonal antibody (mAb) targeting BAFF-R.

Hisham Abdel-Azim, MD, of Children’s Hospital Los Angeles, and his colleagues reported these results in Leukemia.

The researchers first used flow cytometry to detect CD56+ cells in bone marrow and peripheral blood samples from ALL patients. The team discovered these cells were detectable at diagnosis, post-induction, and relapse.

To expand the cells, the researchers cocultured them with artificial antigen-presenting K562 clone 9.mbIL-21 cells. The expanded CD56+ cells demonstrated allogeneic cytotoxicity against ALL cells, even in the absence of antibody.

The addition of a mAb targeting BAFF-R enhanced CD56+ cells’ cytotoxicity against ALL cells. The activity of these CD56+ cells was comparable to that of NK cells derived from healthy patients.

The researchers also compared CD56+CD3- cells to CD56+CD3+ cells and found the CD3- cells exhibited increased levels of activation in antibody-mediated cellular cytotoxicity reactions. The CD56+CD3+ cells were not stimulated by BAFF-R mAbs.

The team then tested the NK cells’ autologous cytotoxicity. And, as in previous experiments, the CD56+ cells from ALL samples demonstrated nonantibody-dependent cytotoxicity and enhanced cytotoxicity in the presence of BAFF-R mAbs.

Finally, the researchers decided to investigate whether the addition of IL-2 or IL-15 could further stimulate CD56+ cells’ cytotoxicity. And while they found that both cytokines did the job, IL-15 proved more successful.

“These results are very promising, with potential as a part of first-line therapy and also as a treatment for eliminating any remaining cancer cells . . . following standard chemotherapy,” Dr Abdel-Azim said. “We anticipate additional preclinical testing and then a clinical trial to evaluate the therapy in children with leukemia.”

An NK cell in action

Credit: Bjorn Onfelt/Dan Davis

In vitro experiments suggest a patient’s own natural killer (NK) cells can be expanded and modified to fight acute lymphoblastic leukemia (ALL).

Researchers successfully expanded CD56+ cells isolated from the bone marrow and peripheral blood of ALL patients.

And these cells exhibited cytotoxicity against the patients’ own ALL cells. The effect was enhanced by the addition of IL-15 and a monoclonal antibody (mAb) targeting BAFF-R.

Hisham Abdel-Azim, MD, of Children’s Hospital Los Angeles, and his colleagues reported these results in Leukemia.

The researchers first used flow cytometry to detect CD56+ cells in bone marrow and peripheral blood samples from ALL patients. The team discovered these cells were detectable at diagnosis, post-induction, and relapse.

To expand the cells, the researchers cocultured them with artificial antigen-presenting K562 clone 9.mbIL-21 cells. The expanded CD56+ cells demonstrated allogeneic cytotoxicity against ALL cells, even in the absence of antibody.

The addition of a mAb targeting BAFF-R enhanced CD56+ cells’ cytotoxicity against ALL cells. The activity of these CD56+ cells was comparable to that of NK cells derived from healthy patients.

The researchers also compared CD56+CD3- cells to CD56+CD3+ cells and found the CD3- cells exhibited increased levels of activation in antibody-mediated cellular cytotoxicity reactions. The CD56+CD3+ cells were not stimulated by BAFF-R mAbs.

The team then tested the NK cells’ autologous cytotoxicity. And, as in previous experiments, the CD56+ cells from ALL samples demonstrated nonantibody-dependent cytotoxicity and enhanced cytotoxicity in the presence of BAFF-R mAbs.

Finally, the researchers decided to investigate whether the addition of IL-2 or IL-15 could further stimulate CD56+ cells’ cytotoxicity. And while they found that both cytokines did the job, IL-15 proved more successful.

“These results are very promising, with potential as a part of first-line therapy and also as a treatment for eliminating any remaining cancer cells . . . following standard chemotherapy,” Dr Abdel-Azim said. “We anticipate additional preclinical testing and then a clinical trial to evaluate the therapy in children with leukemia.”

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

Guidelines developed almost 20 years ago can accurately predict infertility in girls with cancer, according to research published in The Lancet Oncology.

Researchers found the criteria in these guidelines can help healthcare professionals select which girls should be given the option of ovarian tissue cryopreservation.

The team noted that taking the initial samples of ovarian tissue involves a surgical technique that is still relatively experimental.

So it is crucial to accurately predict which patients are most likely to benefit from the procedure and when it can be safely performed.

The guidelines, known as the Edinburgh selection criteria, were instituted in 1996 to help healthcare professionals decide which girls should be given the option of cryopreservation, based on their age, type of cancer treatment, and their chance of cure.

Specifically, patients were required to meet the following criteria:

• Age younger than 35 years
• No previous chemotherapy or radiotherapy if 15 years or older at diagnosis, but mild, non-gonadotoxic chemotherapy was acceptable if a patient was younger than 15
• A realistic chance of surviving for 5 years
• A high risk of premature ovarian insufficiency (>50%)
• Informed consent (from parents and the patient, if possible)
• Negative serology results for HIV, syphilis, and hepatitis B
• Not pregnant and no existing children.

Testing the guidelines

To validate the selection criteria, W. Hamish B. Wallace, MD, of the Royal Hospital for Sick Children in Edinburgh, UK, and his colleagues analyzed 410 female cancer patients who were younger than 18 years at their time of diagnosis.

The patients were treated between January 1, 1996, and June 30, 2012, at the Edinburgh Children’s Cancer Centre, which serves the southeast region of Scotland.

In all, 34 patients (8%) met the Edinburgh selection criteria and were given the option of ovarian tissue cryopreservation before starting cancer treatment. Thirteen patients declined, 21 consented, and 20 had a successful procedure.

The researchers were able to assess ovarian function in 14 of the 20 patients with successful cryopreservation and 6 of the 13 patients who declined the procedure.

Of the 14 evaluable patients who underwent cryopreservation, 6 developed premature ovarian insufficiency at a median age of 13.4 years (range, 12.5–14.6), but 1 of these patients also had a natural pregnancy.

One patient each among the 6 evaluable patients who declined cryopreservation and the 141 evaluable patients who were not offered cryopreservation developed premature ovarian insufficiency.

So, overall, the probability of ovarian insufficiency was significantly higher for patients who met the Edinburgh selection criteria than for those who did not. The 15-year probability was 35% and 1%, respectively (P<0.0001).

The researchers said these results validate the use of the selection criteria, as they can accurately identify patients who will likely develop premature ovarian insufficiency.

“Advances in life-saving treatments mean that more and more young people with cancer are surviving the disease,” Dr Wallace said. “Here, we have an opportunity to help young women to have families of their own when they grow up, if they so choose.”

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

Guidelines developed almost 20 years ago can accurately predict infertility in girls with cancer, according to research published in The Lancet Oncology.

Researchers found the criteria in these guidelines can help healthcare professionals select which girls should be given the option of ovarian tissue cryopreservation.

The team noted that taking the initial samples of ovarian tissue involves a surgical technique that is still relatively experimental.

So it is crucial to accurately predict which patients are most likely to benefit from the procedure and when it can be safely performed.

The guidelines, known as the Edinburgh selection criteria, were instituted in 1996 to help healthcare professionals decide which girls should be given the option of cryopreservation, based on their age, type of cancer treatment, and their chance of cure.

Specifically, patients were required to meet the following criteria:

• Age younger than 35 years
• No previous chemotherapy or radiotherapy if 15 years or older at diagnosis, but mild, non-gonadotoxic chemotherapy was acceptable if a patient was younger than 15
• A realistic chance of surviving for 5 years
• A high risk of premature ovarian insufficiency (>50%)
• Informed consent (from parents and the patient, if possible)
• Negative serology results for HIV, syphilis, and hepatitis B
• Not pregnant and no existing children.

Testing the guidelines

To validate the selection criteria, W. Hamish B. Wallace, MD, of the Royal Hospital for Sick Children in Edinburgh, UK, and his colleagues analyzed 410 female cancer patients who were younger than 18 years at their time of diagnosis.

The patients were treated between January 1, 1996, and June 30, 2012, at the Edinburgh Children’s Cancer Centre, which serves the southeast region of Scotland.

In all, 34 patients (8%) met the Edinburgh selection criteria and were given the option of ovarian tissue cryopreservation before starting cancer treatment. Thirteen patients declined, 21 consented, and 20 had a successful procedure.

The researchers were able to assess ovarian function in 14 of the 20 patients with successful cryopreservation and 6 of the 13 patients who declined the procedure.

Of the 14 evaluable patients who underwent cryopreservation, 6 developed premature ovarian insufficiency at a median age of 13.4 years (range, 12.5–14.6), but 1 of these patients also had a natural pregnancy.

One patient each among the 6 evaluable patients who declined cryopreservation and the 141 evaluable patients who were not offered cryopreservation developed premature ovarian insufficiency.

So, overall, the probability of ovarian insufficiency was significantly higher for patients who met the Edinburgh selection criteria than for those who did not. The 15-year probability was 35% and 1%, respectively (P<0.0001).

The researchers said these results validate the use of the selection criteria, as they can accurately identify patients who will likely develop premature ovarian insufficiency.

“Advances in life-saving treatments mean that more and more young people with cancer are surviving the disease,” Dr Wallace said. “Here, we have an opportunity to help young women to have families of their own when they grow up, if they so choose.”

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

Guidelines developed almost 20 years ago can accurately predict infertility in girls with cancer, according to research published in The Lancet Oncology.

Researchers found the criteria in these guidelines can help healthcare professionals select which girls should be given the option of ovarian tissue cryopreservation.

The team noted that taking the initial samples of ovarian tissue involves a surgical technique that is still relatively experimental.

So it is crucial to accurately predict which patients are most likely to benefit from the procedure and when it can be safely performed.

The guidelines, known as the Edinburgh selection criteria, were instituted in 1996 to help healthcare professionals decide which girls should be given the option of cryopreservation, based on their age, type of cancer treatment, and their chance of cure.

Specifically, patients were required to meet the following criteria:

• Age younger than 35 years
• No previous chemotherapy or radiotherapy if 15 years or older at diagnosis, but mild, non-gonadotoxic chemotherapy was acceptable if a patient was younger than 15
• A realistic chance of surviving for 5 years
• A high risk of premature ovarian insufficiency (>50%)
• Informed consent (from parents and the patient, if possible)
• Negative serology results for HIV, syphilis, and hepatitis B
• Not pregnant and no existing children.

Testing the guidelines

To validate the selection criteria, W. Hamish B. Wallace, MD, of the Royal Hospital for Sick Children in Edinburgh, UK, and his colleagues analyzed 410 female cancer patients who were younger than 18 years at their time of diagnosis.

The patients were treated between January 1, 1996, and June 30, 2012, at the Edinburgh Children’s Cancer Centre, which serves the southeast region of Scotland.

In all, 34 patients (8%) met the Edinburgh selection criteria and were given the option of ovarian tissue cryopreservation before starting cancer treatment. Thirteen patients declined, 21 consented, and 20 had a successful procedure.

The researchers were able to assess ovarian function in 14 of the 20 patients with successful cryopreservation and 6 of the 13 patients who declined the procedure.

Of the 14 evaluable patients who underwent cryopreservation, 6 developed premature ovarian insufficiency at a median age of 13.4 years (range, 12.5–14.6), but 1 of these patients also had a natural pregnancy.

One patient each among the 6 evaluable patients who declined cryopreservation and the 141 evaluable patients who were not offered cryopreservation developed premature ovarian insufficiency.

So, overall, the probability of ovarian insufficiency was significantly higher for patients who met the Edinburgh selection criteria than for those who did not. The 15-year probability was 35% and 1%, respectively (P<0.0001).

The researchers said these results validate the use of the selection criteria, as they can accurately identify patients who will likely develop premature ovarian insufficiency.

“Advances in life-saving treatments mean that more and more young people with cancer are surviving the disease,” Dr Wallace said. “Here, we have an opportunity to help young women to have families of their own when they grow up, if they so choose.”

Nude mouse

Credit: Armin Kübelbeck

Preclinical experiments may have revealed why some cancer patients do not respond to retinoic acid.

Investigators found that a protein known as AEG-1 blocks the effects of retinoic acid in acute myeloid leukemia (AML) and liver cancer.

They also noted that AEG-1 is overexpressed in nearly every cancer type, so these findings could impact the care of countless cancer patients.

The team reported their findings in Cancer Research.

The group’s experiments revealed that AEG-1 binds to retinoid X receptors (RXR), which help regulate cell growth and development. RXR is typically activated by retinoic acid, but the overexpressed AEG-1 proteins found in cancer cells block these signals and help promote tumor growth.

“Our findings are the first to show that AEG-1 interacts with the retinoid X receptor,” said study author Devanand Sarkar, MBBS, PhD, of Virginia Commonwealth University Massey Cancer Center in Richmond.

Specifically, he and his colleagues found that AEG-1 protected hepatocellular carcinoma cells and AML cells from retinoid- and rexinoid-induced cell death.

But in nude mouse models, blocking the production of AEG-1 allowed all-trans retinoic acid to kill hepatocellular carcinoma cells.

The investigators therefore believe that targeting AEG-1 could sensitize AML patients and those with hepatocellular carcinoma to retinoid- and rexinoid-based therapies.

“This research has immediate clinical relevance, such that physicians could begin screening cancer patients for AEG-1 expression levels in order to determine whether retinoic acid should be prescribed,” Dr Sarkar added.

He and his colleagues have been studying AEG-1 for years. They were the first to create a mouse model demonstrating the role of AEG-1 in liver cancer, and they have been working to develop targeted therapies that block AEG-1 production.

The present study expanded their knowledge of the molecular interactions of AEG-1.

“We are continuing to test combination therapies involving AEG-1 inhibition and retinoic acid in animal models, and the initial results are promising,” Dr Sarkar said. “If we continue to see these results in more complex experiments, we hope to eventually propose a phase 1 clinical trial in patients with liver cancer.”

Nude mouse

Credit: Armin Kübelbeck

Preclinical experiments may have revealed why some cancer patients do not respond to retinoic acid.

Investigators found that a protein known as AEG-1 blocks the effects of retinoic acid in acute myeloid leukemia (AML) and liver cancer.

They also noted that AEG-1 is overexpressed in nearly every cancer type, so these findings could impact the care of countless cancer patients.

The team reported their findings in Cancer Research.

The group’s experiments revealed that AEG-1 binds to retinoid X receptors (RXR), which help regulate cell growth and development. RXR is typically activated by retinoic acid, but the overexpressed AEG-1 proteins found in cancer cells block these signals and help promote tumor growth.

“Our findings are the first to show that AEG-1 interacts with the retinoid X receptor,” said study author Devanand Sarkar, MBBS, PhD, of Virginia Commonwealth University Massey Cancer Center in Richmond.

Specifically, he and his colleagues found that AEG-1 protected hepatocellular carcinoma cells and AML cells from retinoid- and rexinoid-induced cell death.

But in nude mouse models, blocking the production of AEG-1 allowed all-trans retinoic acid to kill hepatocellular carcinoma cells.

The investigators therefore believe that targeting AEG-1 could sensitize AML patients and those with hepatocellular carcinoma to retinoid- and rexinoid-based therapies.

“This research has immediate clinical relevance, such that physicians could begin screening cancer patients for AEG-1 expression levels in order to determine whether retinoic acid should be prescribed,” Dr Sarkar added.

He and his colleagues have been studying AEG-1 for years. They were the first to create a mouse model demonstrating the role of AEG-1 in liver cancer, and they have been working to develop targeted therapies that block AEG-1 production.

The present study expanded their knowledge of the molecular interactions of AEG-1.

“We are continuing to test combination therapies involving AEG-1 inhibition and retinoic acid in animal models, and the initial results are promising,” Dr Sarkar said. “If we continue to see these results in more complex experiments, we hope to eventually propose a phase 1 clinical trial in patients with liver cancer.”

Nude mouse

Credit: Armin Kübelbeck

Preclinical experiments may have revealed why some cancer patients do not respond to retinoic acid.

Investigators found that a protein known as AEG-1 blocks the effects of retinoic acid in acute myeloid leukemia (AML) and liver cancer.

They also noted that AEG-1 is overexpressed in nearly every cancer type, so these findings could impact the care of countless cancer patients.

The team reported their findings in Cancer Research.

The group’s experiments revealed that AEG-1 binds to retinoid X receptors (RXR), which help regulate cell growth and development. RXR is typically activated by retinoic acid, but the overexpressed AEG-1 proteins found in cancer cells block these signals and help promote tumor growth.

“Our findings are the first to show that AEG-1 interacts with the retinoid X receptor,” said study author Devanand Sarkar, MBBS, PhD, of Virginia Commonwealth University Massey Cancer Center in Richmond.

Specifically, he and his colleagues found that AEG-1 protected hepatocellular carcinoma cells and AML cells from retinoid- and rexinoid-induced cell death.

But in nude mouse models, blocking the production of AEG-1 allowed all-trans retinoic acid to kill hepatocellular carcinoma cells.

The investigators therefore believe that targeting AEG-1 could sensitize AML patients and those with hepatocellular carcinoma to retinoid- and rexinoid-based therapies.

“This research has immediate clinical relevance, such that physicians could begin screening cancer patients for AEG-1 expression levels in order to determine whether retinoic acid should be prescribed,” Dr Sarkar added.

He and his colleagues have been studying AEG-1 for years. They were the first to create a mouse model demonstrating the role of AEG-1 in liver cancer, and they have been working to develop targeted therapies that block AEG-1 production.

The present study expanded their knowledge of the molecular interactions of AEG-1.

“We are continuing to test combination therapies involving AEG-1 inhibition and retinoic acid in animal models, and the initial results are promising,” Dr Sarkar said. “If we continue to see these results in more complex experiments, we hope to eventually propose a phase 1 clinical trial in patients with liver cancer.”

Recently, Federal Practitioner talked with Benjamin Powers, MD, and Suman Kambhampati, MD, about factors that come into play when treating patients with chronic myelogenous leukemia (CML) and the dramatic improvements in treatment that have been made. To find out more about these factors and improvements, read Blast Phase Chronic Myelogenous Leukemia from the August 2014 issue.

Dr. Powers is a fellow and Dr. Kambhampati is an associate professor of medicine, both in the Department of Internal Medicine, Division of Hematology/Oncology, at the University of Kansas Medical Center in Kansas City, Kansas. Dr. Kambhampati is also a staff physician in the Hematology/Oncology Division at the Kansas City VAMC in Kansas City, Missouri.

Recently, Federal Practitioner talked with Benjamin Powers, MD, and Suman Kambhampati, MD, about factors that come into play when treating patients with chronic myelogenous leukemia (CML) and the dramatic improvements in treatment that have been made. To find out more about these factors and improvements, read Blast Phase Chronic Myelogenous Leukemia from the August 2014 issue.

Dr. Powers is a fellow and Dr. Kambhampati is an associate professor of medicine, both in the Department of Internal Medicine, Division of Hematology/Oncology, at the University of Kansas Medical Center in Kansas City, Kansas. Dr. Kambhampati is also a staff physician in the Hematology/Oncology Division at the Kansas City VAMC in Kansas City, Missouri.

Recently, Federal Practitioner talked with Benjamin Powers, MD, and Suman Kambhampati, MD, about factors that come into play when treating patients with chronic myelogenous leukemia (CML) and the dramatic improvements in treatment that have been made. To find out more about these factors and improvements, read Blast Phase Chronic Myelogenous Leukemia from the August 2014 issue.

Dr. Powers is a fellow and Dr. Kambhampati is an associate professor of medicine, both in the Department of Internal Medicine, Division of Hematology/Oncology, at the University of Kansas Medical Center in Kansas City, Kansas. Dr. Kambhampati is also a staff physician in the Hematology/Oncology Division at the Kansas City VAMC in Kansas City, Missouri.

ALL cells in the bone marrow

Two genes appear to play a key role in acute lymphoblastic leukemia (ALL), particularly for patients who also have Down syndrome.

Researchers found evidence suggesting that 2 in 3 cases of ALL among patients with Down syndrome may be caused by mutations in RAS or JAK2, but the mutations tend not to occur together.

The group therefore believes that if we can begin to identify which of the genes is mutated in ALL patients, we can tailor therapy accordingly.

“We believe our findings are a breakthrough in understanding the underlying causes of leukemia, and, eventually, we hope to design more tailored and effective treatment for this cancer, with less toxic drugs and less side effects,” said study author Dean Nizetic, MD, PhD, a professor at both Queen Mary University of London in the UK and Lee Kong Chian School of Medicine in Singapore.

He and his colleagues reported their findings in Nature Communications.

The researchers conducted full-exome or targeted sequencing in 42 samples from 39 patients with ALL and Down syndrome. The team found similar recurrence rates for driver mutations in RAS (15/42), JAK2 mutations (12/42), and P2RY8-CRLF2 fusions (14/42).

Together, RAS and JAK2 mutations drove two-thirds of the ALL cases, though the mutations were almost completely mutually exclusive (P=0.016).

The researchers also noted that, in two-thirds of patients with relapsed ALL, there was a switch from a primary JAK2- or PTPN11-mutated subclone to a RAS-mutated subclone in relapse.

Moving forward, the team plans to conduct more studies to determine how else RAS and JAK2 might affect children who have ALL, with or without Down syndrome.

ALL cells in the bone marrow

Two genes appear to play a key role in acute lymphoblastic leukemia (ALL), particularly for patients who also have Down syndrome.

Researchers found evidence suggesting that 2 in 3 cases of ALL among patients with Down syndrome may be caused by mutations in RAS or JAK2, but the mutations tend not to occur together.

The group therefore believes that if we can begin to identify which of the genes is mutated in ALL patients, we can tailor therapy accordingly.

“We believe our findings are a breakthrough in understanding the underlying causes of leukemia, and, eventually, we hope to design more tailored and effective treatment for this cancer, with less toxic drugs and less side effects,” said study author Dean Nizetic, MD, PhD, a professor at both Queen Mary University of London in the UK and Lee Kong Chian School of Medicine in Singapore.

He and his colleagues reported their findings in Nature Communications.

The researchers conducted full-exome or targeted sequencing in 42 samples from 39 patients with ALL and Down syndrome. The team found similar recurrence rates for driver mutations in RAS (15/42), JAK2 mutations (12/42), and P2RY8-CRLF2 fusions (14/42).

Together, RAS and JAK2 mutations drove two-thirds of the ALL cases, though the mutations were almost completely mutually exclusive (P=0.016).

The researchers also noted that, in two-thirds of patients with relapsed ALL, there was a switch from a primary JAK2- or PTPN11-mutated subclone to a RAS-mutated subclone in relapse.

Moving forward, the team plans to conduct more studies to determine how else RAS and JAK2 might affect children who have ALL, with or without Down syndrome.

ALL cells in the bone marrow

Two genes appear to play a key role in acute lymphoblastic leukemia (ALL), particularly for patients who also have Down syndrome.

Researchers found evidence suggesting that 2 in 3 cases of ALL among patients with Down syndrome may be caused by mutations in RAS or JAK2, but the mutations tend not to occur together.

The group therefore believes that if we can begin to identify which of the genes is mutated in ALL patients, we can tailor therapy accordingly.

“We believe our findings are a breakthrough in understanding the underlying causes of leukemia, and, eventually, we hope to design more tailored and effective treatment for this cancer, with less toxic drugs and less side effects,” said study author Dean Nizetic, MD, PhD, a professor at both Queen Mary University of London in the UK and Lee Kong Chian School of Medicine in Singapore.

He and his colleagues reported their findings in Nature Communications.

The researchers conducted full-exome or targeted sequencing in 42 samples from 39 patients with ALL and Down syndrome. The team found similar recurrence rates for driver mutations in RAS (15/42), JAK2 mutations (12/42), and P2RY8-CRLF2 fusions (14/42).

Together, RAS and JAK2 mutations drove two-thirds of the ALL cases, though the mutations were almost completely mutually exclusive (P=0.016).

The researchers also noted that, in two-thirds of patients with relapsed ALL, there was a switch from a primary JAK2- or PTPN11-mutated subclone to a RAS-mutated subclone in relapse.

Moving forward, the team plans to conduct more studies to determine how else RAS and JAK2 might affect children who have ALL, with or without Down syndrome.

Preparing pills for a trial

Credit: Esther Dyson

The US Food and Drug Administration (FDA) has granted fast track designation for AG-221 to treat acute myelogenous leukemia (AML) patients with mutated isocitrate dehydrogenase-2 (IDH2).

AG-221 is an IDH2 inhibitor under evaluation in a phase 1 trial of patients with advanced hematologic malignancies.

Results from this trial were presented at the 19th Congress of the European Hematology Association, which took place in Milan in June.

The FDA’s fast track drug development program is designed to expedite clinical development and submission of a new drug application (NDA) for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates meetings between the FDA and the company developing a drug to discuss all aspects of development to support approval. It also affords the developer the opportunity to submit sections of an NDA on a rolling basis as data become available, so the FDA does not have wait for the entire NDA submission before beginning its review.

AG-221 also recently received orphan designation as a treatment for AML. The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders that affect fewer than 200,000 people in the US.

Orphan designation affords the drug’s developer certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

Phase 1 trial results

Thus far in the phase 1 study, AG-221 has proven active and well-tolerated in patients with AML, myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML).

The trial included 35 patients with a median age of 68 years (range, 48-81).

Twenty-seven patients had relapsed/refractory AML, 4 had relapsed/refractory MDS, 2 had untreated AML, 1 had CMML, and 1 had granulocytic sarcoma. Thirty-one patients had R140Q IDH2 mutations, and 4 had R172K IDH2 mutations.

The patients received AG-221 at doses ranging from 30 mg BID to 150 mg QD. Patients completed a median of 1 cycle of treatment (range, <1-5+) and a mean of 2 cycles.

The drug was generally well-tolerated, largely prompting grade 1 or 2 adverse events. Grade 3 or higher events included thrombocytopenia (n=3), anemia (n=1), febrile neutropenia (n=3), sepsis (n=3), diarrhea (n=1), fatigue (n=1), leukocytosis (n=2), neutropenia (n=1), and rash (n=1).

Four patients had serious events possibly related to treatment. One patient had grade 3 confusion and grade 5 respiratory failure. One patient had grade 3 leukocytosis, grade 3 anorexia, and grade 1 nausea. One patient had grade 3 diarrhea. And 1 patient had grade 3 leukocytosis.

Twenty-five patients were evaluable for response. There were 6 complete responses (CRs), 2 CRs with incomplete platelet recovery, 1 CR with incomplete hematologic recovery, and 5 partial responses. Five patients had stable disease, and 6 had progressive disease.

The most responses occurred among patients who received AG-221 at 50 mg BID, and most responses occurred in cycle 1.

Twelve of the 14 responses are ongoing. Of the 8 patients who achieved a CR or CR with incomplete platelet recovery, 5 have lasted more than 2.5 months (range, 1-4+ months). And the 5 patients with stable disease remain on study.

This study is sponsored by Agios Pharmaceuticals Inc., the company developing AG-221 in collaboration with Celgene.

Preparing pills for a trial

Credit: Esther Dyson

The US Food and Drug Administration (FDA) has granted fast track designation for AG-221 to treat acute myelogenous leukemia (AML) patients with mutated isocitrate dehydrogenase-2 (IDH2).

AG-221 is an IDH2 inhibitor under evaluation in a phase 1 trial of patients with advanced hematologic malignancies.

Results from this trial were presented at the 19th Congress of the European Hematology Association, which took place in Milan in June.

The FDA’s fast track drug development program is designed to expedite clinical development and submission of a new drug application (NDA) for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates meetings between the FDA and the company developing a drug to discuss all aspects of development to support approval. It also affords the developer the opportunity to submit sections of an NDA on a rolling basis as data become available, so the FDA does not have wait for the entire NDA submission before beginning its review.

AG-221 also recently received orphan designation as a treatment for AML. The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders that affect fewer than 200,000 people in the US.

Orphan designation affords the drug’s developer certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

Phase 1 trial results

Thus far in the phase 1 study, AG-221 has proven active and well-tolerated in patients with AML, myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML).

The trial included 35 patients with a median age of 68 years (range, 48-81).

Twenty-seven patients had relapsed/refractory AML, 4 had relapsed/refractory MDS, 2 had untreated AML, 1 had CMML, and 1 had granulocytic sarcoma. Thirty-one patients had R140Q IDH2 mutations, and 4 had R172K IDH2 mutations.

The patients received AG-221 at doses ranging from 30 mg BID to 150 mg QD. Patients completed a median of 1 cycle of treatment (range, <1-5+) and a mean of 2 cycles.

The drug was generally well-tolerated, largely prompting grade 1 or 2 adverse events. Grade 3 or higher events included thrombocytopenia (n=3), anemia (n=1), febrile neutropenia (n=3), sepsis (n=3), diarrhea (n=1), fatigue (n=1), leukocytosis (n=2), neutropenia (n=1), and rash (n=1).

Four patients had serious events possibly related to treatment. One patient had grade 3 confusion and grade 5 respiratory failure. One patient had grade 3 leukocytosis, grade 3 anorexia, and grade 1 nausea. One patient had grade 3 diarrhea. And 1 patient had grade 3 leukocytosis.

Twenty-five patients were evaluable for response. There were 6 complete responses (CRs), 2 CRs with incomplete platelet recovery, 1 CR with incomplete hematologic recovery, and 5 partial responses. Five patients had stable disease, and 6 had progressive disease.

The most responses occurred among patients who received AG-221 at 50 mg BID, and most responses occurred in cycle 1.

Twelve of the 14 responses are ongoing. Of the 8 patients who achieved a CR or CR with incomplete platelet recovery, 5 have lasted more than 2.5 months (range, 1-4+ months). And the 5 patients with stable disease remain on study.

This study is sponsored by Agios Pharmaceuticals Inc., the company developing AG-221 in collaboration with Celgene.

Preparing pills for a trial

Credit: Esther Dyson

The US Food and Drug Administration (FDA) has granted fast track designation for AG-221 to treat acute myelogenous leukemia (AML) patients with mutated isocitrate dehydrogenase-2 (IDH2).

AG-221 is an IDH2 inhibitor under evaluation in a phase 1 trial of patients with advanced hematologic malignancies.

Results from this trial were presented at the 19th Congress of the European Hematology Association, which took place in Milan in June.

The FDA’s fast track drug development program is designed to expedite clinical development and submission of a new drug application (NDA) for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates meetings between the FDA and the company developing a drug to discuss all aspects of development to support approval. It also affords the developer the opportunity to submit sections of an NDA on a rolling basis as data become available, so the FDA does not have wait for the entire NDA submission before beginning its review.

AG-221 also recently received orphan designation as a treatment for AML. The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders that affect fewer than 200,000 people in the US.

Orphan designation affords the drug’s developer certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

Phase 1 trial results

Thus far in the phase 1 study, AG-221 has proven active and well-tolerated in patients with AML, myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML).

The trial included 35 patients with a median age of 68 years (range, 48-81).

Twenty-seven patients had relapsed/refractory AML, 4 had relapsed/refractory MDS, 2 had untreated AML, 1 had CMML, and 1 had granulocytic sarcoma. Thirty-one patients had R140Q IDH2 mutations, and 4 had R172K IDH2 mutations.

The patients received AG-221 at doses ranging from 30 mg BID to 150 mg QD. Patients completed a median of 1 cycle of treatment (range, <1-5+) and a mean of 2 cycles.

The drug was generally well-tolerated, largely prompting grade 1 or 2 adverse events. Grade 3 or higher events included thrombocytopenia (n=3), anemia (n=1), febrile neutropenia (n=3), sepsis (n=3), diarrhea (n=1), fatigue (n=1), leukocytosis (n=2), neutropenia (n=1), and rash (n=1).

Four patients had serious events possibly related to treatment. One patient had grade 3 confusion and grade 5 respiratory failure. One patient had grade 3 leukocytosis, grade 3 anorexia, and grade 1 nausea. One patient had grade 3 diarrhea. And 1 patient had grade 3 leukocytosis.

Twenty-five patients were evaluable for response. There were 6 complete responses (CRs), 2 CRs with incomplete platelet recovery, 1 CR with incomplete hematologic recovery, and 5 partial responses. Five patients had stable disease, and 6 had progressive disease.

The most responses occurred among patients who received AG-221 at 50 mg BID, and most responses occurred in cycle 1.

Twelve of the 14 responses are ongoing. Of the 8 patients who achieved a CR or CR with incomplete platelet recovery, 5 have lasted more than 2.5 months (range, 1-4+ months). And the 5 patients with stable disease remain on study.

This study is sponsored by Agios Pharmaceuticals Inc., the company developing AG-221 in collaboration with Celgene.

Woman on a scale

A higher body mass index (BMI) increases the risk of developing 10 common cancers, according to a study of more than 5 million adults in the UK.

The research revealed an association between BMI and leukemia, as well as certain solid tumor malignancies, but no association for multiple myeloma or non-Hodgkin lymphoma.

Krishnan Bhaskaran, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and his colleagues reported these findings in The Lancet.

“The number of people who are overweight or obese is rapidly increasing, both in the UK and worldwide,” Dr Bhaskaran said. “It is well recognized that this is likely to cause more diabetes and cardiovascular disease. Our results show that, if these trends continue, we can also expect to see substantially more cancers as a result.”

Using data from general practitioner records in the UK’s Clinical Practice Research Datalink, Dr Bhaskaran and his colleagues identified 5.24 million individuals aged 16 and older who were cancer-free and had been followed for an average of 7.5 years.

The researchers assessed the subjects’ risk of developing 22 of the most common cancers, which represent 90% of the cancers diagnosed in the UK. The team evaluated cancer risk according to BMI after adjusting for individual factors such as age, sex, smoking status, and socioeconomic status.

A total of 166,955 people developed 1 of the 22 cancers studied during the follow-up period.

BMI was associated with 17 of the cancer types—leukemia and melanoma, as well as cancers of the oral cavity, esophagus, stomach, colon, liver, gallbladder, pancreas, lung, breast, cervix, uterus, ovaries, prostate, kidney, and thyroid.

BMI was not associated with non-Hodgkin lymphoma, multiple myeloma, or cancers of the rectum, bladder, or brain/central nervous system.

Each 5 kg/m² increase in BMI was clearly linked with a higher risk of cancers of the uterus (62% increase), gallbladder (31%), kidney (25%), cervix (10%), thyroid (9%), and leukemia (9%).

Higher BMI also increased the overall risk of liver (19% increase), colon (10%), ovarian (9%), and breast cancers (5%), but the effects on these cancers varied by underlying BMI and by factors such as sex and menopausal status.

Even within normal BMI ranges, a higher BMI was associated with an increased risk of some cancers.

On the other hand, there was some evidence that subjects with a high BMI were at a slightly reduced risk of prostate cancer and premenopausal breast cancer.

“There was a lot of variation in the effects of BMI on different cancers, ” Dr Bhaskaran explained. “For example, risk of cancer of the uterus increased substantially at higher body mass index. For other cancers, we saw more modest increases in risk, or no effect at all.”

“For some cancers, like breast cancer occurring in younger women before the menopause, there even seemed to be a lower risk at higher BMI. This variation tells us that BMI must affect cancer risk through a number of different processes, depending on the cancer type.”

In a linked comment article, Peter Campbell, PhD, of the American Cancer Society in Atlanta, Georgia, said this research underscores the need for policy changes to reduce the incidence of obesity and being overweight in the UK and the rest of the world.

Woman on a scale

A higher body mass index (BMI) increases the risk of developing 10 common cancers, according to a study of more than 5 million adults in the UK.

The research revealed an association between BMI and leukemia, as well as certain solid tumor malignancies, but no association for multiple myeloma or non-Hodgkin lymphoma.

Krishnan Bhaskaran, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and his colleagues reported these findings in The Lancet.

“The number of people who are overweight or obese is rapidly increasing, both in the UK and worldwide,” Dr Bhaskaran said. “It is well recognized that this is likely to cause more diabetes and cardiovascular disease. Our results show that, if these trends continue, we can also expect to see substantially more cancers as a result.”

Using data from general practitioner records in the UK’s Clinical Practice Research Datalink, Dr Bhaskaran and his colleagues identified 5.24 million individuals aged 16 and older who were cancer-free and had been followed for an average of 7.5 years.

The researchers assessed the subjects’ risk of developing 22 of the most common cancers, which represent 90% of the cancers diagnosed in the UK. The team evaluated cancer risk according to BMI after adjusting for individual factors such as age, sex, smoking status, and socioeconomic status.

A total of 166,955 people developed 1 of the 22 cancers studied during the follow-up period.

BMI was associated with 17 of the cancer types—leukemia and melanoma, as well as cancers of the oral cavity, esophagus, stomach, colon, liver, gallbladder, pancreas, lung, breast, cervix, uterus, ovaries, prostate, kidney, and thyroid.

BMI was not associated with non-Hodgkin lymphoma, multiple myeloma, or cancers of the rectum, bladder, or brain/central nervous system.

Each 5 kg/m² increase in BMI was clearly linked with a higher risk of cancers of the uterus (62% increase), gallbladder (31%), kidney (25%), cervix (10%), thyroid (9%), and leukemia (9%).

Higher BMI also increased the overall risk of liver (19% increase), colon (10%), ovarian (9%), and breast cancers (5%), but the effects on these cancers varied by underlying BMI and by factors such as sex and menopausal status.

Even within normal BMI ranges, a higher BMI was associated with an increased risk of some cancers.

On the other hand, there was some evidence that subjects with a high BMI were at a slightly reduced risk of prostate cancer and premenopausal breast cancer.

“There was a lot of variation in the effects of BMI on different cancers, ” Dr Bhaskaran explained. “For example, risk of cancer of the uterus increased substantially at higher body mass index. For other cancers, we saw more modest increases in risk, or no effect at all.”

“For some cancers, like breast cancer occurring in younger women before the menopause, there even seemed to be a lower risk at higher BMI. This variation tells us that BMI must affect cancer risk through a number of different processes, depending on the cancer type.”

In a linked comment article, Peter Campbell, PhD, of the American Cancer Society in Atlanta, Georgia, said this research underscores the need for policy changes to reduce the incidence of obesity and being overweight in the UK and the rest of the world.

Woman on a scale

A higher body mass index (BMI) increases the risk of developing 10 common cancers, according to a study of more than 5 million adults in the UK.

The research revealed an association between BMI and leukemia, as well as certain solid tumor malignancies, but no association for multiple myeloma or non-Hodgkin lymphoma.

Krishnan Bhaskaran, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and his colleagues reported these findings in The Lancet.

“The number of people who are overweight or obese is rapidly increasing, both in the UK and worldwide,” Dr Bhaskaran said. “It is well recognized that this is likely to cause more diabetes and cardiovascular disease. Our results show that, if these trends continue, we can also expect to see substantially more cancers as a result.”

Using data from general practitioner records in the UK’s Clinical Practice Research Datalink, Dr Bhaskaran and his colleagues identified 5.24 million individuals aged 16 and older who were cancer-free and had been followed for an average of 7.5 years.

The researchers assessed the subjects’ risk of developing 22 of the most common cancers, which represent 90% of the cancers diagnosed in the UK. The team evaluated cancer risk according to BMI after adjusting for individual factors such as age, sex, smoking status, and socioeconomic status.

A total of 166,955 people developed 1 of the 22 cancers studied during the follow-up period.

BMI was associated with 17 of the cancer types—leukemia and melanoma, as well as cancers of the oral cavity, esophagus, stomach, colon, liver, gallbladder, pancreas, lung, breast, cervix, uterus, ovaries, prostate, kidney, and thyroid.

BMI was not associated with non-Hodgkin lymphoma, multiple myeloma, or cancers of the rectum, bladder, or brain/central nervous system.

Each 5 kg/m² increase in BMI was clearly linked with a higher risk of cancers of the uterus (62% increase), gallbladder (31%), kidney (25%), cervix (10%), thyroid (9%), and leukemia (9%).

Higher BMI also increased the overall risk of liver (19% increase), colon (10%), ovarian (9%), and breast cancers (5%), but the effects on these cancers varied by underlying BMI and by factors such as sex and menopausal status.

Even within normal BMI ranges, a higher BMI was associated with an increased risk of some cancers.

On the other hand, there was some evidence that subjects with a high BMI were at a slightly reduced risk of prostate cancer and premenopausal breast cancer.

“There was a lot of variation in the effects of BMI on different cancers, ” Dr Bhaskaran explained. “For example, risk of cancer of the uterus increased substantially at higher body mass index. For other cancers, we saw more modest increases in risk, or no effect at all.”

“For some cancers, like breast cancer occurring in younger women before the menopause, there even seemed to be a lower risk at higher BMI. This variation tells us that BMI must affect cancer risk through a number of different processes, depending on the cancer type.”

In a linked comment article, Peter Campbell, PhD, of the American Cancer Society in Atlanta, Georgia, said this research underscores the need for policy changes to reduce the incidence of obesity and being overweight in the UK and the rest of the world.

Child with leukemia

Credit: Bill Branson

Childhood cancer survivors are no more likely than their cancer-free peers to adhere to healthy living guidelines, according to a study published in the Journal of Cancer Survivorship.

Survivors were less likely to be smokers and had a lower average body mass index (BMI).

But there were no significant differences between survivors and cancer-free control subjects with regard to overall diet, physical activity, or alcohol consumption.

Chloe Berdan, of Promedica in Toledo, Ohio, and her colleagues uncovered these results by examining data from the Chicago Healthy Living Study.

The team assessed adherence to American Cancer Society Guidelines on Nutrition and Physical Activity via interviews with 431 childhood cancer survivors and 361 control subjects who never had cancer. The survivors, ages 18 to 59, were all diagnosed with a malignant cancer before their 21st birthdays.

There were no significant differences in sex or race between survivors and controls. Survivors were younger than controls (28.4±7.8 vs 29.6± 8.3 years, P=0.04) and had less education (14.0±2.0 vs 14.4±2.0 years, P=0.01).

Overall, there was no significant difference between survivors and control subjects in adhering to the American Cancer Society guidelines.

Survivors and controls also had similar scores for several individual measures, including alcohol consumption, overall physical activity, overall diet, the servings of fruits/vegetables consumed, and the consumption of red/processed meat.

However, survivors were significantly less likely than controls to be smokers—11.4% vs 17.5% (P=0.02). Survivors had, on average, a BMI of about 1.2 kg/m² lower than controls (P=0.01). And survivors consumed significantly less fiber than controls—9.2±3.5 vs 9.7±3.8 kcal (P=0.05).

Only about 1 in 10 survivors (10.2%) met fiber recommendations, 17.7% ate 5 fruits or vegetables per day, and 46.2% met the red/processed meat recommendation of less than 18 oz per week. On average, survivors scored under 50% for the quality of their diets.

Survivors were better at meeting the goal of at least 5 hours of moderate activity per week (60.5%) than to sticking to any of the other guidelines.

About 36% of survivors were within a healthy BMI range, 2.9% were underweight, 28.9% were overweight, and 32.4% were obese.

The 0.7% of survivors who adhered fully to the guidelines tended to be women, non-smokers, and people with a good view of their own health.

“There is still much room for improvement in educating and encouraging survivors to follow healthier diets and lifestyles,” Berdan said. “Adopting such behavior during early adulthood may have a lasting impact on their quality of life and overall survival.”

Child with leukemia

Credit: Bill Branson

Childhood cancer survivors are no more likely than their cancer-free peers to adhere to healthy living guidelines, according to a study published in the Journal of Cancer Survivorship.

Survivors were less likely to be smokers and had a lower average body mass index (BMI).

But there were no significant differences between survivors and cancer-free control subjects with regard to overall diet, physical activity, or alcohol consumption.

Chloe Berdan, of Promedica in Toledo, Ohio, and her colleagues uncovered these results by examining data from the Chicago Healthy Living Study.

The team assessed adherence to American Cancer Society Guidelines on Nutrition and Physical Activity via interviews with 431 childhood cancer survivors and 361 control subjects who never had cancer. The survivors, ages 18 to 59, were all diagnosed with a malignant cancer before their 21st birthdays.

There were no significant differences in sex or race between survivors and controls. Survivors were younger than controls (28.4±7.8 vs 29.6± 8.3 years, P=0.04) and had less education (14.0±2.0 vs 14.4±2.0 years, P=0.01).

Overall, there was no significant difference between survivors and control subjects in adhering to the American Cancer Society guidelines.

Survivors and controls also had similar scores for several individual measures, including alcohol consumption, overall physical activity, overall diet, the servings of fruits/vegetables consumed, and the consumption of red/processed meat.

However, survivors were significantly less likely than controls to be smokers—11.4% vs 17.5% (P=0.02). Survivors had, on average, a BMI of about 1.2 kg/m² lower than controls (P=0.01). And survivors consumed significantly less fiber than controls—9.2±3.5 vs 9.7±3.8 kcal (P=0.05).

Only about 1 in 10 survivors (10.2%) met fiber recommendations, 17.7% ate 5 fruits or vegetables per day, and 46.2% met the red/processed meat recommendation of less than 18 oz per week. On average, survivors scored under 50% for the quality of their diets.

Survivors were better at meeting the goal of at least 5 hours of moderate activity per week (60.5%) than to sticking to any of the other guidelines.

About 36% of survivors were within a healthy BMI range, 2.9% were underweight, 28.9% were overweight, and 32.4% were obese.

The 0.7% of survivors who adhered fully to the guidelines tended to be women, non-smokers, and people with a good view of their own health.

“There is still much room for improvement in educating and encouraging survivors to follow healthier diets and lifestyles,” Berdan said. “Adopting such behavior during early adulthood may have a lasting impact on their quality of life and overall survival.”

Child with leukemia

Credit: Bill Branson

Childhood cancer survivors are no more likely than their cancer-free peers to adhere to healthy living guidelines, according to a study published in the Journal of Cancer Survivorship.

Survivors were less likely to be smokers and had a lower average body mass index (BMI).

But there were no significant differences between survivors and cancer-free control subjects with regard to overall diet, physical activity, or alcohol consumption.

Chloe Berdan, of Promedica in Toledo, Ohio, and her colleagues uncovered these results by examining data from the Chicago Healthy Living Study.

The team assessed adherence to American Cancer Society Guidelines on Nutrition and Physical Activity via interviews with 431 childhood cancer survivors and 361 control subjects who never had cancer. The survivors, ages 18 to 59, were all diagnosed with a malignant cancer before their 21st birthdays.

There were no significant differences in sex or race between survivors and controls. Survivors were younger than controls (28.4±7.8 vs 29.6± 8.3 years, P=0.04) and had less education (14.0±2.0 vs 14.4±2.0 years, P=0.01).

Overall, there was no significant difference between survivors and control subjects in adhering to the American Cancer Society guidelines.

Survivors and controls also had similar scores for several individual measures, including alcohol consumption, overall physical activity, overall diet, the servings of fruits/vegetables consumed, and the consumption of red/processed meat.

However, survivors were significantly less likely than controls to be smokers—11.4% vs 17.5% (P=0.02). Survivors had, on average, a BMI of about 1.2 kg/m² lower than controls (P=0.01). And survivors consumed significantly less fiber than controls—9.2±3.5 vs 9.7±3.8 kcal (P=0.05).

Only about 1 in 10 survivors (10.2%) met fiber recommendations, 17.7% ate 5 fruits or vegetables per day, and 46.2% met the red/processed meat recommendation of less than 18 oz per week. On average, survivors scored under 50% for the quality of their diets.

Survivors were better at meeting the goal of at least 5 hours of moderate activity per week (60.5%) than to sticking to any of the other guidelines.

About 36% of survivors were within a healthy BMI range, 2.9% were underweight, 28.9% were overweight, and 32.4% were obese.

The 0.7% of survivors who adhered fully to the guidelines tended to be women, non-smokers, and people with a good view of their own health.

“There is still much room for improvement in educating and encouraging survivors to follow healthier diets and lifestyles,” Berdan said. “Adopting such behavior during early adulthood may have a lasting impact on their quality of life and overall survival.”