Leukemia, Myelodysplasia, Transplantation

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

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

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

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

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

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

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

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

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

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

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

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

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

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

By 2020:

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

By 2025:

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

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

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

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

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

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

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

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

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

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

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

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

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

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

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

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

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

By 2020:

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

By 2025:

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

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

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

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

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

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

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

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

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

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

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

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

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

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

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

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

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

By 2020:

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

By 2025:

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

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

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

Laurence Cooper, MD, PhD

Photo courtesy of MDACC

NEW YORK—Researchers have used a nonviral approach to create chimeric antigen receptor (CAR) T cells and tested these cells in safety trials.

Patients with advanced lymphoma or leukemia were infused with the nonvirally modified CD19-directed CAR T cells after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

Eighty-six percent of autologous HSCT recipients were alive 24 months after infusion, and 53% of allogeneic HSCT recipients were alive with a median follow-up of 6.5 months.

“Gratifyingly, the patients have not demonstrated any acute or late toxicity to these CAR T-cell infusions,” said Laurence Cooper, MD, PhD, formerly of MD Anderson Cancer Center (MDACC) in Houston, Texas, and now with Ziopharm Oncology.

Dr Cooper presented these results at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Some of the technology he described was conducted at MDACC. Dr Cooper is currently a visiting scientist there and will continue to supervise the development of this technology.

Dr Cooper said the appeal of this nonviral approach, which is a modified Sleeping Beauty approach, “is it essentially avoids the complexity of making a virus, a lentivirus or a retrovirus, it can be done at quite low cost, and really allows for a nimbleness to this system.”

Using a simple blood draw of 200 cc of peripheral blood—the process does not require apheresis—the T cells can be expanded on a feeder cell layer and genetically reprogrammed.

Sleeping Beauty system

The researchers reprogrammed the T cells using a 2-plasmid Sleeping Beauty system, which is a transposon/transposase system.

The transposon DNA plasmid codes for the cargo load, which, in this case, is the CAR. At the same time, the transposase DNA plasmid is electroporated, “which is really the secret sauce of the transposition event,” Dr Cooper explained.

After electroporation, the transposon/transposase are co-cultured with K562-derived artificial antigen-presenting cells (aAPC) and expanded with the integrated transposon of K562-aAPC. In this case, CD19 is on the aAPC.

CD19 is co-expressed with other co-stimulatory molecules, CD86 and 4-1BB ligand.

In addition, the researchers added a molecule of interleukin 15 that’s sewn in frame to the Fc region of an immunoglobulin that then activates the T cell in the context of these co-stimulatory molecules.

The T cells that have stable integrants of the CAR grow out over time. And those that have transient expression of the CAR die by neglect.

“By day 14, most of the T cells have the CAR sewn into the genome and are stably expressed,” Dr Cooper said.

The CAR used for these safety trials at MDACC targets CD19 and uses mouse scFv held in frame with an immunoglobulin 4 Fc (IgG4Fc) stalk.

It’s tunneled through the T-cell membrane and has 2 costimulatory molecules, signal 1 delivered by phosphorylation of the immunoreceptor tyrosine-based activation motif in CD3ζ and signal 2 by the costimulatory domain CD28.

The researchers tested the CD19 CARs in 2 clinical settings—one with T cells that were patient-derived and infused after autologous HSCT, and the second with T cells that were derived from a third party and infused after allogeneic HSCT.

Infusion after autologous HSCT

The researchers first tried the CARs in 7 non-Hodgkin lymphoma patients who had an autologous HSCT. Their median age was 52 (range, 36-61).

Five patients received a starting CAR T-cell dose of 5x10⁸ cells/m², and 2 received 5x10⁹ cells/m².

Six patients (86%) remain alive and are in complete remission (CR) at a median follow-up of 24 months.

Infusion after allogeneic HSCT

The researchers expanded the investigation to a wider cohort of 19 patients who had undergone allogeneic HSCT.

Seventeen patients had advanced CD19-positive acute lymphoblastic leukemia, and 2 had non-Hodgkin lymphoma. Their median age was 35 (range, 21-56).

All patients were on graft-versus-host disease (GVHD) prophylaxis with tacrolimus at the time of CAR infusion. A subset of these allogeneic transplant patients had haploidentical donors rather than matched sibling donors.

Five patients received a CAR T-cell dose of 10⁶, 6 patients received 10⁷, 5 received 5x10⁷, and 3 received 5x10⁸ cells/m² based on recipient body surface area.

Fifty-eight percent of patients (11/19) achieved a CR, and 10 remain alive a median of 6.5 months after CAR T-cell infusion.

Three patients developed GVHD, 1 with steroid-refractory acute liver disease, 1 with grade 2 acute skin disease, and 1 with chronic limited skin disease. The incidence of GVHD was lower than historical controls at MDACC, Dr Cooper said.

“[G]ratifyingly, in this clinical setting of minimal disease, patients did not have any acute or late toxicity from these infusions,” he added.

And the rate of cytomegalovirus reactivation after CAR T-cell infusion was 24%, compared with 41% for patients after transplant at MDACC without CAR T-cell infusion.

Eight patients received haploidentical HSCT followed by CAR T-cell infusion, and 75% (6/8) remain in CR.

Persistence of infused T cells

The researchers used 2 forms of PCR—qPCR and droplet PCR—to map the fate of the CARs.

“Roughly speaking, for these patients, and this is in line with the literature, in terms of those T cells that are activated through CD28 in contrast to 4-1BB, these T cells are, on average, living about 28 or so days post-infusion,” Dr Cooper noted.

He said this is similar to results observed with CARs being tested at the National Cancer Institute and Memorial Sloan-Kettering Cancer Center.

Laurence Cooper, MD, PhD

Photo courtesy of MDACC

NEW YORK—Researchers have used a nonviral approach to create chimeric antigen receptor (CAR) T cells and tested these cells in safety trials.

Patients with advanced lymphoma or leukemia were infused with the nonvirally modified CD19-directed CAR T cells after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

Eighty-six percent of autologous HSCT recipients were alive 24 months after infusion, and 53% of allogeneic HSCT recipients were alive with a median follow-up of 6.5 months.

“Gratifyingly, the patients have not demonstrated any acute or late toxicity to these CAR T-cell infusions,” said Laurence Cooper, MD, PhD, formerly of MD Anderson Cancer Center (MDACC) in Houston, Texas, and now with Ziopharm Oncology.

Dr Cooper presented these results at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Some of the technology he described was conducted at MDACC. Dr Cooper is currently a visiting scientist there and will continue to supervise the development of this technology.

Dr Cooper said the appeal of this nonviral approach, which is a modified Sleeping Beauty approach, “is it essentially avoids the complexity of making a virus, a lentivirus or a retrovirus, it can be done at quite low cost, and really allows for a nimbleness to this system.”

Using a simple blood draw of 200 cc of peripheral blood—the process does not require apheresis—the T cells can be expanded on a feeder cell layer and genetically reprogrammed.

Sleeping Beauty system

The researchers reprogrammed the T cells using a 2-plasmid Sleeping Beauty system, which is a transposon/transposase system.

The transposon DNA plasmid codes for the cargo load, which, in this case, is the CAR. At the same time, the transposase DNA plasmid is electroporated, “which is really the secret sauce of the transposition event,” Dr Cooper explained.

After electroporation, the transposon/transposase are co-cultured with K562-derived artificial antigen-presenting cells (aAPC) and expanded with the integrated transposon of K562-aAPC. In this case, CD19 is on the aAPC.

CD19 is co-expressed with other co-stimulatory molecules, CD86 and 4-1BB ligand.

In addition, the researchers added a molecule of interleukin 15 that’s sewn in frame to the Fc region of an immunoglobulin that then activates the T cell in the context of these co-stimulatory molecules.

The T cells that have stable integrants of the CAR grow out over time. And those that have transient expression of the CAR die by neglect.

“By day 14, most of the T cells have the CAR sewn into the genome and are stably expressed,” Dr Cooper said.

The CAR used for these safety trials at MDACC targets CD19 and uses mouse scFv held in frame with an immunoglobulin 4 Fc (IgG4Fc) stalk.

It’s tunneled through the T-cell membrane and has 2 costimulatory molecules, signal 1 delivered by phosphorylation of the immunoreceptor tyrosine-based activation motif in CD3ζ and signal 2 by the costimulatory domain CD28.

The researchers tested the CD19 CARs in 2 clinical settings—one with T cells that were patient-derived and infused after autologous HSCT, and the second with T cells that were derived from a third party and infused after allogeneic HSCT.

Infusion after autologous HSCT

The researchers first tried the CARs in 7 non-Hodgkin lymphoma patients who had an autologous HSCT. Their median age was 52 (range, 36-61).

Five patients received a starting CAR T-cell dose of 5x10⁸ cells/m², and 2 received 5x10⁹ cells/m².

Six patients (86%) remain alive and are in complete remission (CR) at a median follow-up of 24 months.

Infusion after allogeneic HSCT

The researchers expanded the investigation to a wider cohort of 19 patients who had undergone allogeneic HSCT.

Seventeen patients had advanced CD19-positive acute lymphoblastic leukemia, and 2 had non-Hodgkin lymphoma. Their median age was 35 (range, 21-56).

All patients were on graft-versus-host disease (GVHD) prophylaxis with tacrolimus at the time of CAR infusion. A subset of these allogeneic transplant patients had haploidentical donors rather than matched sibling donors.

Five patients received a CAR T-cell dose of 10⁶, 6 patients received 10⁷, 5 received 5x10⁷, and 3 received 5x10⁸ cells/m² based on recipient body surface area.

Fifty-eight percent of patients (11/19) achieved a CR, and 10 remain alive a median of 6.5 months after CAR T-cell infusion.

Three patients developed GVHD, 1 with steroid-refractory acute liver disease, 1 with grade 2 acute skin disease, and 1 with chronic limited skin disease. The incidence of GVHD was lower than historical controls at MDACC, Dr Cooper said.

“[G]ratifyingly, in this clinical setting of minimal disease, patients did not have any acute or late toxicity from these infusions,” he added.

And the rate of cytomegalovirus reactivation after CAR T-cell infusion was 24%, compared with 41% for patients after transplant at MDACC without CAR T-cell infusion.

Eight patients received haploidentical HSCT followed by CAR T-cell infusion, and 75% (6/8) remain in CR.

Persistence of infused T cells

The researchers used 2 forms of PCR—qPCR and droplet PCR—to map the fate of the CARs.

“Roughly speaking, for these patients, and this is in line with the literature, in terms of those T cells that are activated through CD28 in contrast to 4-1BB, these T cells are, on average, living about 28 or so days post-infusion,” Dr Cooper noted.

He said this is similar to results observed with CARs being tested at the National Cancer Institute and Memorial Sloan-Kettering Cancer Center.

Laurence Cooper, MD, PhD

Photo courtesy of MDACC

NEW YORK—Researchers have used a nonviral approach to create chimeric antigen receptor (CAR) T cells and tested these cells in safety trials.

Patients with advanced lymphoma or leukemia were infused with the nonvirally modified CD19-directed CAR T cells after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

Eighty-six percent of autologous HSCT recipients were alive 24 months after infusion, and 53% of allogeneic HSCT recipients were alive with a median follow-up of 6.5 months.

“Gratifyingly, the patients have not demonstrated any acute or late toxicity to these CAR T-cell infusions,” said Laurence Cooper, MD, PhD, formerly of MD Anderson Cancer Center (MDACC) in Houston, Texas, and now with Ziopharm Oncology.

Dr Cooper presented these results at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Some of the technology he described was conducted at MDACC. Dr Cooper is currently a visiting scientist there and will continue to supervise the development of this technology.

Dr Cooper said the appeal of this nonviral approach, which is a modified Sleeping Beauty approach, “is it essentially avoids the complexity of making a virus, a lentivirus or a retrovirus, it can be done at quite low cost, and really allows for a nimbleness to this system.”

Using a simple blood draw of 200 cc of peripheral blood—the process does not require apheresis—the T cells can be expanded on a feeder cell layer and genetically reprogrammed.

Sleeping Beauty system

The researchers reprogrammed the T cells using a 2-plasmid Sleeping Beauty system, which is a transposon/transposase system.

The transposon DNA plasmid codes for the cargo load, which, in this case, is the CAR. At the same time, the transposase DNA plasmid is electroporated, “which is really the secret sauce of the transposition event,” Dr Cooper explained.

After electroporation, the transposon/transposase are co-cultured with K562-derived artificial antigen-presenting cells (aAPC) and expanded with the integrated transposon of K562-aAPC. In this case, CD19 is on the aAPC.

CD19 is co-expressed with other co-stimulatory molecules, CD86 and 4-1BB ligand.

In addition, the researchers added a molecule of interleukin 15 that’s sewn in frame to the Fc region of an immunoglobulin that then activates the T cell in the context of these co-stimulatory molecules.

The T cells that have stable integrants of the CAR grow out over time. And those that have transient expression of the CAR die by neglect.

“By day 14, most of the T cells have the CAR sewn into the genome and are stably expressed,” Dr Cooper said.

The CAR used for these safety trials at MDACC targets CD19 and uses mouse scFv held in frame with an immunoglobulin 4 Fc (IgG4Fc) stalk.

It’s tunneled through the T-cell membrane and has 2 costimulatory molecules, signal 1 delivered by phosphorylation of the immunoreceptor tyrosine-based activation motif in CD3ζ and signal 2 by the costimulatory domain CD28.

The researchers tested the CD19 CARs in 2 clinical settings—one with T cells that were patient-derived and infused after autologous HSCT, and the second with T cells that were derived from a third party and infused after allogeneic HSCT.

Infusion after autologous HSCT

The researchers first tried the CARs in 7 non-Hodgkin lymphoma patients who had an autologous HSCT. Their median age was 52 (range, 36-61).

Five patients received a starting CAR T-cell dose of 5x10⁸ cells/m², and 2 received 5x10⁹ cells/m².

Six patients (86%) remain alive and are in complete remission (CR) at a median follow-up of 24 months.

Infusion after allogeneic HSCT

The researchers expanded the investigation to a wider cohort of 19 patients who had undergone allogeneic HSCT.

Seventeen patients had advanced CD19-positive acute lymphoblastic leukemia, and 2 had non-Hodgkin lymphoma. Their median age was 35 (range, 21-56).

All patients were on graft-versus-host disease (GVHD) prophylaxis with tacrolimus at the time of CAR infusion. A subset of these allogeneic transplant patients had haploidentical donors rather than matched sibling donors.

Five patients received a CAR T-cell dose of 10⁶, 6 patients received 10⁷, 5 received 5x10⁷, and 3 received 5x10⁸ cells/m² based on recipient body surface area.

Fifty-eight percent of patients (11/19) achieved a CR, and 10 remain alive a median of 6.5 months after CAR T-cell infusion.

Three patients developed GVHD, 1 with steroid-refractory acute liver disease, 1 with grade 2 acute skin disease, and 1 with chronic limited skin disease. The incidence of GVHD was lower than historical controls at MDACC, Dr Cooper said.

“[G]ratifyingly, in this clinical setting of minimal disease, patients did not have any acute or late toxicity from these infusions,” he added.

And the rate of cytomegalovirus reactivation after CAR T-cell infusion was 24%, compared with 41% for patients after transplant at MDACC without CAR T-cell infusion.

Eight patients received haploidentical HSCT followed by CAR T-cell infusion, and 75% (6/8) remain in CR.

Persistence of infused T cells

The researchers used 2 forms of PCR—qPCR and droplet PCR—to map the fate of the CARs.

“Roughly speaking, for these patients, and this is in line with the literature, in terms of those T cells that are activated through CD28 in contrast to 4-1BB, these T cells are, on average, living about 28 or so days post-infusion,” Dr Cooper noted.

He said this is similar to results observed with CARs being tested at the National Cancer Institute and Memorial Sloan-Kettering Cancer Center.

Doctor and patient

Photo by Logan Tuttle

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

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

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

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

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

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

Problem-solving

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

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

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

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

Understanding biology

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

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

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

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

Improving quality of life

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

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

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

Doctor and patient

Photo by Logan Tuttle

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

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

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

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

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

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

Problem-solving

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

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

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

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

Understanding biology

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

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

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

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

Improving quality of life

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

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

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

Doctor and patient

Photo by Logan Tuttle

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

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

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

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

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

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

Problem-solving

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

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

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

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

Understanding biology

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

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

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

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

Improving quality of life

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

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

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

Micrograph showing AML

Image by Lance Liotta

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

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

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

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

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

AML-001 trial

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

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

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

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

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

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

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

Micrograph showing AML

Image by Lance Liotta

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

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

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

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

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

AML-001 trial

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

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

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

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

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

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

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

Micrograph showing AML

Image by Lance Liotta

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

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

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

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

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

AML-001 trial

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

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

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

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

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

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

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

Pregnant woman

Photo by Nina Matthews

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

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

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

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

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

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

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

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

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

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

Mental development

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

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

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

Premature birth

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

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

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

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

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

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

Cardiac function

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

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

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

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

Next steps

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

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

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

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

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

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

Pregnant woman

Photo by Nina Matthews

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

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

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

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

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

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

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

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

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

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

Mental development

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

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

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

Premature birth

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

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

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

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

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

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

Cardiac function

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

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

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

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

Next steps

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

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

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

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

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

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

Pregnant woman

Photo by Nina Matthews

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

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

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

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

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

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

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

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

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

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

Mental development

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

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

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

Premature birth

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

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

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

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

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

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

Cardiac function

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

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

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

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

Next steps

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

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

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

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

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

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

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”

Micrograph showing CLL

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).

NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.

This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.

Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.

NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.

NICE’s 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.

Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Clinical effectiveness

The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.

For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.

Cost-effectiveness

Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.

Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.

Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.

The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).

Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).

Micrograph showing CLL

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).

NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.

This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.

Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.

NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.

NICE’s 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.

Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Clinical effectiveness

The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.

For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.

Cost-effectiveness

Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.

Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.

Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.

The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).

Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).

Micrograph showing CLL

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).

NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.

This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.

Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.

NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.

NICE’s 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.

Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Clinical effectiveness

The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.

For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.

Cost-effectiveness

Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.

Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.

Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.

The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).

Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).

Wendell Lim, PhD

Photo courtesy of UCSF

Researchers have reported progress in developing an “on/off switch” to temper the over-active immune response and severe toxicities that can result from chimeric antigen receptor (CAR) T-cell therapy.

The team created CAR T cells that are “off” by default, homing to CD19-expressing cancer cells but remaining inactive until a small molecule is administered.

This system effectively targeted leukemia and lymphoma cells in preclinical experiments.

But the researchers said it’s not ready for clinical testing, as the small-molecule “trigger” is expensive and lasts only 4 hours.

Still, the team believes this type of CAR T-cell therapy could eventually help doctors gradually increase the immune response to treatment and therefore avoid toxicities such as cytokine release syndrome and tumor lysis syndrome.

Wendell Lim, PhD, of University of California, San Francisco, and his colleagues described this work in Science.

“T cells are really powerful beasts, and they can be lethal when they’re activated,” Dr Lim said. “We’ve needed a remote control system that retains the power of these engineered T cells but allows us to communicate specifically with them and manage them while they’re in the body.”

To that end, he and his colleagues created a CAR that requires both an antigen and a small molecule for activation. They dubbed it the “ON-switch CAR.”

ON-switch CAR

The researchers explained that the ON-switch CAR consists of 2 parts that assemble in a small molecule-dependent manner.

Part 1 consists of a CD8α signal sequence, Myc epitope, anti-CD19 single-chain variable fragment, CD8α hinge and transmembrane domain, 4-1BB costimulatory motif, and FK506 Binding Protein (FKBP) domain for heterodimerization.

Part 2 consists of the ectodomain of DNAX-activating protein 10 (DAP10) for homodimerization, CD8α transmembrane domain for membrane anchoring, 4-1BB costimulatory motif, T2089L mutant of FKBP-rapamycin binding (FRB*) domain, T-cell receptor CD3ζ signaling chain, and mCherry tag.

The FKBP and FRB* domains heterodimerize in the presence of the rapamycin analog AP21967, referred to as the “rapalog.”

The researchers conducted in vitro experiments with this ON-switch CAR in cells expressing CD19 (K562, Raji, and Daudi).

The ON-switch CAR T cells homed to CD19-expressing cells but did nothing else until the rapalog was added. Once the rapalog was added, CD19-expressing cells were killed off in a dose-dependent manner.

The team observed similar results in mice with leukemia. Leukemia cells (K562) were selectively eliminated by the ON-switch CARs only after the rapalog had been administered.

Dr Lim stressed that this work should be considered a proof of principle, as the rapalog has too short a half-life to be clinically useful. Nevertheless, he believes the research provides the foundation for practical remote control of CAR T cells.

Members of his lab are exploring other techniques to accomplish this goal, such as controlling CAR T-cell activation with light.

The team is also working to reduce side effects of CAR T-cell therapy by introducing multiple CARs into T cells so the cells will respond to multiple characteristics that are distinctive to an individual patient’s tumor, rather than to a single protein that may also be found on normal cells.

“That we can engineer CAR T cells to have slightly different, quite powerful effects—even if for a subset of patients or for certain types of cancer—is really remarkable,” Dr Lim said. “And this is just the tip of the iceberg.”

Wendell Lim, PhD

Photo courtesy of UCSF

Researchers have reported progress in developing an “on/off switch” to temper the over-active immune response and severe toxicities that can result from chimeric antigen receptor (CAR) T-cell therapy.

The team created CAR T cells that are “off” by default, homing to CD19-expressing cancer cells but remaining inactive until a small molecule is administered.

This system effectively targeted leukemia and lymphoma cells in preclinical experiments.

But the researchers said it’s not ready for clinical testing, as the small-molecule “trigger” is expensive and lasts only 4 hours.

Still, the team believes this type of CAR T-cell therapy could eventually help doctors gradually increase the immune response to treatment and therefore avoid toxicities such as cytokine release syndrome and tumor lysis syndrome.

Wendell Lim, PhD, of University of California, San Francisco, and his colleagues described this work in Science.

“T cells are really powerful beasts, and they can be lethal when they’re activated,” Dr Lim said. “We’ve needed a remote control system that retains the power of these engineered T cells but allows us to communicate specifically with them and manage them while they’re in the body.”

To that end, he and his colleagues created a CAR that requires both an antigen and a small molecule for activation. They dubbed it the “ON-switch CAR.”

ON-switch CAR

The researchers explained that the ON-switch CAR consists of 2 parts that assemble in a small molecule-dependent manner.

Part 1 consists of a CD8α signal sequence, Myc epitope, anti-CD19 single-chain variable fragment, CD8α hinge and transmembrane domain, 4-1BB costimulatory motif, and FK506 Binding Protein (FKBP) domain for heterodimerization.

Part 2 consists of the ectodomain of DNAX-activating protein 10 (DAP10) for homodimerization, CD8α transmembrane domain for membrane anchoring, 4-1BB costimulatory motif, T2089L mutant of FKBP-rapamycin binding (FRB*) domain, T-cell receptor CD3ζ signaling chain, and mCherry tag.

The FKBP and FRB* domains heterodimerize in the presence of the rapamycin analog AP21967, referred to as the “rapalog.”

The researchers conducted in vitro experiments with this ON-switch CAR in cells expressing CD19 (K562, Raji, and Daudi).

The ON-switch CAR T cells homed to CD19-expressing cells but did nothing else until the rapalog was added. Once the rapalog was added, CD19-expressing cells were killed off in a dose-dependent manner.

The team observed similar results in mice with leukemia. Leukemia cells (K562) were selectively eliminated by the ON-switch CARs only after the rapalog had been administered.

Dr Lim stressed that this work should be considered a proof of principle, as the rapalog has too short a half-life to be clinically useful. Nevertheless, he believes the research provides the foundation for practical remote control of CAR T cells.

Members of his lab are exploring other techniques to accomplish this goal, such as controlling CAR T-cell activation with light.

The team is also working to reduce side effects of CAR T-cell therapy by introducing multiple CARs into T cells so the cells will respond to multiple characteristics that are distinctive to an individual patient’s tumor, rather than to a single protein that may also be found on normal cells.

“That we can engineer CAR T cells to have slightly different, quite powerful effects—even if for a subset of patients or for certain types of cancer—is really remarkable,” Dr Lim said. “And this is just the tip of the iceberg.”

Wendell Lim, PhD

Photo courtesy of UCSF

Researchers have reported progress in developing an “on/off switch” to temper the over-active immune response and severe toxicities that can result from chimeric antigen receptor (CAR) T-cell therapy.

The team created CAR T cells that are “off” by default, homing to CD19-expressing cancer cells but remaining inactive until a small molecule is administered.

This system effectively targeted leukemia and lymphoma cells in preclinical experiments.

But the researchers said it’s not ready for clinical testing, as the small-molecule “trigger” is expensive and lasts only 4 hours.

Still, the team believes this type of CAR T-cell therapy could eventually help doctors gradually increase the immune response to treatment and therefore avoid toxicities such as cytokine release syndrome and tumor lysis syndrome.

Wendell Lim, PhD, of University of California, San Francisco, and his colleagues described this work in Science.

“T cells are really powerful beasts, and they can be lethal when they’re activated,” Dr Lim said. “We’ve needed a remote control system that retains the power of these engineered T cells but allows us to communicate specifically with them and manage them while they’re in the body.”

To that end, he and his colleagues created a CAR that requires both an antigen and a small molecule for activation. They dubbed it the “ON-switch CAR.”

ON-switch CAR

The researchers explained that the ON-switch CAR consists of 2 parts that assemble in a small molecule-dependent manner.

Part 1 consists of a CD8α signal sequence, Myc epitope, anti-CD19 single-chain variable fragment, CD8α hinge and transmembrane domain, 4-1BB costimulatory motif, and FK506 Binding Protein (FKBP) domain for heterodimerization.

Part 2 consists of the ectodomain of DNAX-activating protein 10 (DAP10) for homodimerization, CD8α transmembrane domain for membrane anchoring, 4-1BB costimulatory motif, T2089L mutant of FKBP-rapamycin binding (FRB*) domain, T-cell receptor CD3ζ signaling chain, and mCherry tag.

The FKBP and FRB* domains heterodimerize in the presence of the rapamycin analog AP21967, referred to as the “rapalog.”

The researchers conducted in vitro experiments with this ON-switch CAR in cells expressing CD19 (K562, Raji, and Daudi).

The ON-switch CAR T cells homed to CD19-expressing cells but did nothing else until the rapalog was added. Once the rapalog was added, CD19-expressing cells were killed off in a dose-dependent manner.

The team observed similar results in mice with leukemia. Leukemia cells (K562) were selectively eliminated by the ON-switch CARs only after the rapalog had been administered.

Dr Lim stressed that this work should be considered a proof of principle, as the rapalog has too short a half-life to be clinically useful. Nevertheless, he believes the research provides the foundation for practical remote control of CAR T cells.

Members of his lab are exploring other techniques to accomplish this goal, such as controlling CAR T-cell activation with light.

The team is also working to reduce side effects of CAR T-cell therapy by introducing multiple CARs into T cells so the cells will respond to multiple characteristics that are distinctive to an individual patient’s tumor, rather than to a single protein that may also be found on normal cells.

“That we can engineer CAR T cells to have slightly different, quite powerful effects—even if for a subset of patients or for certain types of cancer—is really remarkable,” Dr Lim said. “And this is just the tip of the iceberg.”

Young cancer patient

Photo by Bill Branson

Results of a small study reveal the material hardships families experience when a child is undergoing cancer treatment.

Researchers surveyed 99 families of children with cancer.

Six months after the child’s diagnosis, 29% of the families reported having at least one household material hardship, such as food, housing, or energy insecurity.

Twenty percent of the families had reported having such hardships at the time of the child’s diagnosis.

Kira Bona, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts, and her colleagues reported results from this survey in Pediatric Blood & Cancer.

The researchers surveyed 99 families of pediatric cancer patients treated at Dana-Farber/Boston Children’s, first within a month of diagnosis and then 6 months later.

At diagnosis, 20% of the families were low-income, which was defined as 200% of the federal poverty level. Six months later, an additional 12% suffered income losses that pushed them into the low-income group.

At 6 months, 25% of the families said they had lost more than 40% of their household income due to treatment-related work disruptions. A total of 56% of adults who supported their families experienced a disruption of their work.

This included 15% of parents who either quit their jobs or were laid off as a result of their child’s illness, as well as 37% of respondents who cut their hours or took a leave of absence. Thirty-four percent of these individuals were paid during their leave.

At 6 months, 29% of families said they had at least one material hardship. Twenty percent reported food insecurity, 17% reported energy insecurity, and 8% reported housing insecurity.*

These findings surprised researchers, who said they expected lower levels of need at their center because it provides psychosocial support for patients and has resource specialists to help families facing financial difficulties.

“What it says is that even at a well-resourced, large referral center, about a third of families are reporting food, housing, or energy insecurity 6 months into treatment,” Dr Bona said. “If anything, the numbers in our study are an underestimate of what might be seen at less well-resourced institutions, which was somewhat surprising to us.”

By focusing on specific material hardships, which can be addressed through governmental or philanthropic support, the researchers hope they have identified variables that are easier for clinicians to ameliorate than overall income.

Dr Bona said subsequent research will examine whether material hardship has the same effect on patient outcomes as low-income status.

“If household material hardship is linked to poorer outcomes in pediatric oncology, just like income is, then we can design interventions to fix food, housing, and energy insecurity,” she said. “It’s not clear what you do about income in a clinical setting.”

*Definitions for household material hardships were as follows.

Food insecurity was measured via the US Household Food Security Survey Module: Six-Item Short Form, which includes questions to asses if respondents:

• sometimes/often do not have enough food to eat
• sometimes/often cannot afford to eat balanced meals
• sometimes/often worry about having enough money to buy food, etc.

Families met the definition for housing insecurity if they reported any of the following:

• crowding (defined as >2 people per bedroom in the home)
• multiple moves (>1 move in the prior year)
• doubling up (having to live with other people, even temporarily, because of financial difficulties in the past 6 months).

Families met the definition for energy insecurity if, in the prior 6 months, they had experienced any of the following:

• received a letter threatening to shut off the gas/electricity/oil to their house because they had not paid the bills
• had the gas/electric/oil company shut off electricity or refused to deliver oil/gas because they had not paid the bills
• had any days that their home was not heated/cooled because they couldn’t pay the bills
• had ever used a cooking stove to heat their home because they couldn’t pay the bills.

Young cancer patient

Photo by Bill Branson

Results of a small study reveal the material hardships families experience when a child is undergoing cancer treatment.

Researchers surveyed 99 families of children with cancer.

Six months after the child’s diagnosis, 29% of the families reported having at least one household material hardship, such as food, housing, or energy insecurity.

Twenty percent of the families had reported having such hardships at the time of the child’s diagnosis.

Kira Bona, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts, and her colleagues reported results from this survey in Pediatric Blood & Cancer.

The researchers surveyed 99 families of pediatric cancer patients treated at Dana-Farber/Boston Children’s, first within a month of diagnosis and then 6 months later.

At diagnosis, 20% of the families were low-income, which was defined as 200% of the federal poverty level. Six months later, an additional 12% suffered income losses that pushed them into the low-income group.

At 6 months, 25% of the families said they had lost more than 40% of their household income due to treatment-related work disruptions. A total of 56% of adults who supported their families experienced a disruption of their work.

This included 15% of parents who either quit their jobs or were laid off as a result of their child’s illness, as well as 37% of respondents who cut their hours or took a leave of absence. Thirty-four percent of these individuals were paid during their leave.

At 6 months, 29% of families said they had at least one material hardship. Twenty percent reported food insecurity, 17% reported energy insecurity, and 8% reported housing insecurity.*

These findings surprised researchers, who said they expected lower levels of need at their center because it provides psychosocial support for patients and has resource specialists to help families facing financial difficulties.

“What it says is that even at a well-resourced, large referral center, about a third of families are reporting food, housing, or energy insecurity 6 months into treatment,” Dr Bona said. “If anything, the numbers in our study are an underestimate of what might be seen at less well-resourced institutions, which was somewhat surprising to us.”

By focusing on specific material hardships, which can be addressed through governmental or philanthropic support, the researchers hope they have identified variables that are easier for clinicians to ameliorate than overall income.

Dr Bona said subsequent research will examine whether material hardship has the same effect on patient outcomes as low-income status.

“If household material hardship is linked to poorer outcomes in pediatric oncology, just like income is, then we can design interventions to fix food, housing, and energy insecurity,” she said. “It’s not clear what you do about income in a clinical setting.”

*Definitions for household material hardships were as follows.

Food insecurity was measured via the US Household Food Security Survey Module: Six-Item Short Form, which includes questions to asses if respondents:

• sometimes/often do not have enough food to eat
• sometimes/often cannot afford to eat balanced meals
• sometimes/often worry about having enough money to buy food, etc.

Families met the definition for housing insecurity if they reported any of the following:

• crowding (defined as >2 people per bedroom in the home)
• multiple moves (>1 move in the prior year)
• doubling up (having to live with other people, even temporarily, because of financial difficulties in the past 6 months).

Families met the definition for energy insecurity if, in the prior 6 months, they had experienced any of the following:

• received a letter threatening to shut off the gas/electricity/oil to their house because they had not paid the bills
• had the gas/electric/oil company shut off electricity or refused to deliver oil/gas because they had not paid the bills
• had any days that their home was not heated/cooled because they couldn’t pay the bills
• had ever used a cooking stove to heat their home because they couldn’t pay the bills.

Young cancer patient

Photo by Bill Branson

Results of a small study reveal the material hardships families experience when a child is undergoing cancer treatment.

Researchers surveyed 99 families of children with cancer.

Six months after the child’s diagnosis, 29% of the families reported having at least one household material hardship, such as food, housing, or energy insecurity.

Twenty percent of the families had reported having such hardships at the time of the child’s diagnosis.

Kira Bona, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts, and her colleagues reported results from this survey in Pediatric Blood & Cancer.

The researchers surveyed 99 families of pediatric cancer patients treated at Dana-Farber/Boston Children’s, first within a month of diagnosis and then 6 months later.

At diagnosis, 20% of the families were low-income, which was defined as 200% of the federal poverty level. Six months later, an additional 12% suffered income losses that pushed them into the low-income group.

At 6 months, 25% of the families said they had lost more than 40% of their household income due to treatment-related work disruptions. A total of 56% of adults who supported their families experienced a disruption of their work.

This included 15% of parents who either quit their jobs or were laid off as a result of their child’s illness, as well as 37% of respondents who cut their hours or took a leave of absence. Thirty-four percent of these individuals were paid during their leave.

At 6 months, 29% of families said they had at least one material hardship. Twenty percent reported food insecurity, 17% reported energy insecurity, and 8% reported housing insecurity.*

These findings surprised researchers, who said they expected lower levels of need at their center because it provides psychosocial support for patients and has resource specialists to help families facing financial difficulties.

“What it says is that even at a well-resourced, large referral center, about a third of families are reporting food, housing, or energy insecurity 6 months into treatment,” Dr Bona said. “If anything, the numbers in our study are an underestimate of what might be seen at less well-resourced institutions, which was somewhat surprising to us.”

By focusing on specific material hardships, which can be addressed through governmental or philanthropic support, the researchers hope they have identified variables that are easier for clinicians to ameliorate than overall income.

Dr Bona said subsequent research will examine whether material hardship has the same effect on patient outcomes as low-income status.

“If household material hardship is linked to poorer outcomes in pediatric oncology, just like income is, then we can design interventions to fix food, housing, and energy insecurity,” she said. “It’s not clear what you do about income in a clinical setting.”

*Definitions for household material hardships were as follows.

Food insecurity was measured via the US Household Food Security Survey Module: Six-Item Short Form, which includes questions to asses if respondents:

• sometimes/often do not have enough food to eat
• sometimes/often cannot afford to eat balanced meals
• sometimes/often worry about having enough money to buy food, etc.

Families met the definition for housing insecurity if they reported any of the following:

• crowding (defined as >2 people per bedroom in the home)
• multiple moves (>1 move in the prior year)
• doubling up (having to live with other people, even temporarily, because of financial difficulties in the past 6 months).

Families met the definition for energy insecurity if, in the prior 6 months, they had experienced any of the following:

• received a letter threatening to shut off the gas/electricity/oil to their house because they had not paid the bills
• had the gas/electric/oil company shut off electricity or refused to deliver oil/gas because they had not paid the bills
• had any days that their home was not heated/cooled because they couldn’t pay the bills
• had ever used a cooking stove to heat their home because they couldn’t pay the bills.