Less intensive childhood cancer therapy reduces late toxicities, deaths

CHICAGO – Decades-old efforts to reduce the intensity of therapies for childhood cancers are paying off, resulting in significant declines in late all-cause mortality among those who survive 5-years after a cancer diagnosis, investigators report.

For patients treated in the 1970s for childhood cancers, the 15-year cumulative mortality rate was 3.1%, compared with 2.4% for those treated in the 80’s, and 1.9% for those treated in the 90’s, reported Dr. Gregory T. Armstrong from St. Jude’s Children’s Research Hospital, Memphis.

Neil Osterweil

“The improvement in cure rate of childhood cancer is really one of the success stories of modern medicine. If you go back to the 1960s, less than 30-40% of children were surviving cancer. Currently, over 82% of children will become 5-year survivors,” he said at a press briefing at the annual meeting of the American Society of Clinical Oncology.

“However, these 5-year survivors, as they move forward, are still at risk for late events and early mortality. As shown previously for these 5-year survivors, even after hitting the 5-year turning point, 18% will be deceased 30 years from diagnosis,” he said.

But efforts to reduce the intensity of therapy without compromising the quality of care appear to be having their effect, as seen in long-term follow-up results from patients in the Childhood Cancer Survivor Study.

The study, initiated in 1994, follows a retrospective cohort of children treated at 31 US and Canadian hospitals from 1970 through 1999 for common childhood malignancies, including leukemias, lymphomas, central nervous system malignancies, Wilms tumor, neuroblastoma, and sarcomas of soft tissues and/or bones.

The investigators looked at follow-up data on 34,033 cohort members who were alive 5 years after diagnosis, and for whom there was detailed information on the cumulative chemotherapy dose exposures and organ-specific radiotherapy dosimetry.

At a median follow-up of 21 years, 3958 (12%) of the cohort had died, and of this group 1618 (41%) were deemed to have died from health-related causes, including late effects of cancer therapy, such as cardiovascular causes (243 deaths), pulmonary problems (136), and second malignancies (751 deaths).

In each category and in all-cause mortality, there were significant reductions in the cumulative incidence of deaths over time. For example: all-cause mortality declined from 12.4% during the 1970-74 era to 6.0 from 1990-94 (P < .001), deaths from second cancers dropped from 1.8% to 1.0% over the same period (P < .001), cardiac-related deaths fell from 0.5% to 0.1% (P = .001), and pulmonary deaths declined from 0.4% to 0.1% (P = .02).

In a multivariable analysis adjusted for age at diagnosis, sex, and diagnosis and follow-up time, each 5-year interval was associated with a significant reduction in deaths from other health related causes (relative risk [RR] 0.86), subsequent neoplasm (RR 0.83), cardiac causes (RR 0.77), and pulmonary disease (RR 0.77). The confidence intervals for all variables indicated statistical significance.

Additionally, when they looked at specific cancers, they saw declines in cardiac mortality for acute lymphoblastic leukemia, Hodgkin’s lymphoma, and Wilms tumor, and a decrease in second malignancies for patients with Wilms tumor.

The reductions in deaths paralleled changes in clinical practice, notably reductions in the use of cranial radiotherapy for patients with acute lymphoblastic leukemia from 86% of patients in the 70s to 22% in the 90s, as well as reductions in abdominal radiation given to children with Wilms tumor (from 77% to 49%, respectively) and in chest radiation given for Hodgkin’s lymphoma (from 96% to 77%).

Dr. Michael P. Link, professor in pediatric cancer at Stanford University School of Medicine, the invited discussant, said the study results provide important lessons for clinicians treating adult as well as childhood cancers. He noted that reductions in the intensity of therapy and limiting exposures results in decreases in late organ toxicity, secondary cancers, and mortality.

“The translation and modification of therapy designed to reduce exposures into clinically significant reductions in all-cause late mortality is a gratifying validation of three decades of refining our therapies to accomplish the same number of cures while lowering the cost of cure,” he said.

The Childhood Cancer Survivor Study is funded by the National Institutes of Health. Dr. Armstrong and Dr. Link reported no relevant disclosures.

CHICAGO – Decades-old efforts to reduce the intensity of therapies for childhood cancers are paying off, resulting in significant declines in late all-cause mortality among those who survive 5-years after a cancer diagnosis, investigators report.

For patients treated in the 1970s for childhood cancers, the 15-year cumulative mortality rate was 3.1%, compared with 2.4% for those treated in the 80’s, and 1.9% for those treated in the 90’s, reported Dr. Gregory T. Armstrong from St. Jude’s Children’s Research Hospital, Memphis.

Neil Osterweil

“The improvement in cure rate of childhood cancer is really one of the success stories of modern medicine. If you go back to the 1960s, less than 30-40% of children were surviving cancer. Currently, over 82% of children will become 5-year survivors,” he said at a press briefing at the annual meeting of the American Society of Clinical Oncology.

“However, these 5-year survivors, as they move forward, are still at risk for late events and early mortality. As shown previously for these 5-year survivors, even after hitting the 5-year turning point, 18% will be deceased 30 years from diagnosis,” he said.

But efforts to reduce the intensity of therapy without compromising the quality of care appear to be having their effect, as seen in long-term follow-up results from patients in the Childhood Cancer Survivor Study.

The study, initiated in 1994, follows a retrospective cohort of children treated at 31 US and Canadian hospitals from 1970 through 1999 for common childhood malignancies, including leukemias, lymphomas, central nervous system malignancies, Wilms tumor, neuroblastoma, and sarcomas of soft tissues and/or bones.

The investigators looked at follow-up data on 34,033 cohort members who were alive 5 years after diagnosis, and for whom there was detailed information on the cumulative chemotherapy dose exposures and organ-specific radiotherapy dosimetry.

At a median follow-up of 21 years, 3958 (12%) of the cohort had died, and of this group 1618 (41%) were deemed to have died from health-related causes, including late effects of cancer therapy, such as cardiovascular causes (243 deaths), pulmonary problems (136), and second malignancies (751 deaths).

In each category and in all-cause mortality, there were significant reductions in the cumulative incidence of deaths over time. For example: all-cause mortality declined from 12.4% during the 1970-74 era to 6.0 from 1990-94 (P < .001), deaths from second cancers dropped from 1.8% to 1.0% over the same period (P < .001), cardiac-related deaths fell from 0.5% to 0.1% (P = .001), and pulmonary deaths declined from 0.4% to 0.1% (P = .02).

In a multivariable analysis adjusted for age at diagnosis, sex, and diagnosis and follow-up time, each 5-year interval was associated with a significant reduction in deaths from other health related causes (relative risk [RR] 0.86), subsequent neoplasm (RR 0.83), cardiac causes (RR 0.77), and pulmonary disease (RR 0.77). The confidence intervals for all variables indicated statistical significance.

Additionally, when they looked at specific cancers, they saw declines in cardiac mortality for acute lymphoblastic leukemia, Hodgkin’s lymphoma, and Wilms tumor, and a decrease in second malignancies for patients with Wilms tumor.

The reductions in deaths paralleled changes in clinical practice, notably reductions in the use of cranial radiotherapy for patients with acute lymphoblastic leukemia from 86% of patients in the 70s to 22% in the 90s, as well as reductions in abdominal radiation given to children with Wilms tumor (from 77% to 49%, respectively) and in chest radiation given for Hodgkin’s lymphoma (from 96% to 77%).

Dr. Michael P. Link, professor in pediatric cancer at Stanford University School of Medicine, the invited discussant, said the study results provide important lessons for clinicians treating adult as well as childhood cancers. He noted that reductions in the intensity of therapy and limiting exposures results in decreases in late organ toxicity, secondary cancers, and mortality.

“The translation and modification of therapy designed to reduce exposures into clinically significant reductions in all-cause late mortality is a gratifying validation of three decades of refining our therapies to accomplish the same number of cures while lowering the cost of cure,” he said.

The Childhood Cancer Survivor Study is funded by the National Institutes of Health. Dr. Armstrong and Dr. Link reported no relevant disclosures.

CHICAGO – Decades-old efforts to reduce the intensity of therapies for childhood cancers are paying off, resulting in significant declines in late all-cause mortality among those who survive 5-years after a cancer diagnosis, investigators report.

For patients treated in the 1970s for childhood cancers, the 15-year cumulative mortality rate was 3.1%, compared with 2.4% for those treated in the 80’s, and 1.9% for those treated in the 90’s, reported Dr. Gregory T. Armstrong from St. Jude’s Children’s Research Hospital, Memphis.

Neil Osterweil

“The improvement in cure rate of childhood cancer is really one of the success stories of modern medicine. If you go back to the 1960s, less than 30-40% of children were surviving cancer. Currently, over 82% of children will become 5-year survivors,” he said at a press briefing at the annual meeting of the American Society of Clinical Oncology.

“However, these 5-year survivors, as they move forward, are still at risk for late events and early mortality. As shown previously for these 5-year survivors, even after hitting the 5-year turning point, 18% will be deceased 30 years from diagnosis,” he said.

But efforts to reduce the intensity of therapy without compromising the quality of care appear to be having their effect, as seen in long-term follow-up results from patients in the Childhood Cancer Survivor Study.

The study, initiated in 1994, follows a retrospective cohort of children treated at 31 US and Canadian hospitals from 1970 through 1999 for common childhood malignancies, including leukemias, lymphomas, central nervous system malignancies, Wilms tumor, neuroblastoma, and sarcomas of soft tissues and/or bones.

The investigators looked at follow-up data on 34,033 cohort members who were alive 5 years after diagnosis, and for whom there was detailed information on the cumulative chemotherapy dose exposures and organ-specific radiotherapy dosimetry.

At a median follow-up of 21 years, 3958 (12%) of the cohort had died, and of this group 1618 (41%) were deemed to have died from health-related causes, including late effects of cancer therapy, such as cardiovascular causes (243 deaths), pulmonary problems (136), and second malignancies (751 deaths).

In each category and in all-cause mortality, there were significant reductions in the cumulative incidence of deaths over time. For example: all-cause mortality declined from 12.4% during the 1970-74 era to 6.0 from 1990-94 (P < .001), deaths from second cancers dropped from 1.8% to 1.0% over the same period (P < .001), cardiac-related deaths fell from 0.5% to 0.1% (P = .001), and pulmonary deaths declined from 0.4% to 0.1% (P = .02).

In a multivariable analysis adjusted for age at diagnosis, sex, and diagnosis and follow-up time, each 5-year interval was associated with a significant reduction in deaths from other health related causes (relative risk [RR] 0.86), subsequent neoplasm (RR 0.83), cardiac causes (RR 0.77), and pulmonary disease (RR 0.77). The confidence intervals for all variables indicated statistical significance.

Additionally, when they looked at specific cancers, they saw declines in cardiac mortality for acute lymphoblastic leukemia, Hodgkin’s lymphoma, and Wilms tumor, and a decrease in second malignancies for patients with Wilms tumor.

The reductions in deaths paralleled changes in clinical practice, notably reductions in the use of cranial radiotherapy for patients with acute lymphoblastic leukemia from 86% of patients in the 70s to 22% in the 90s, as well as reductions in abdominal radiation given to children with Wilms tumor (from 77% to 49%, respectively) and in chest radiation given for Hodgkin’s lymphoma (from 96% to 77%).

Dr. Michael P. Link, professor in pediatric cancer at Stanford University School of Medicine, the invited discussant, said the study results provide important lessons for clinicians treating adult as well as childhood cancers. He noted that reductions in the intensity of therapy and limiting exposures results in decreases in late organ toxicity, secondary cancers, and mortality.

“The translation and modification of therapy designed to reduce exposures into clinically significant reductions in all-cause late mortality is a gratifying validation of three decades of refining our therapies to accomplish the same number of cures while lowering the cost of cure,” he said.

The Childhood Cancer Survivor Study is funded by the National Institutes of Health. Dr. Armstrong and Dr. Link reported no relevant disclosures.