Page 71 - 2014 Printable Abstract Book
P. 71
tolerance to therapy is necessary. Relevant variables are the total and fractional dosage of irradiation,
dosage rate, overall treatment time, machine energy, treatment volume, and dosage distribution.
Radiation damage is produced by some combination of parenchymal cell loss and injury to the underlying
vasculature. Initial tissue recovery results mainly from parenchymal cell repopulation. The progressive
component of damage is the arteriolar-capillary fibrosis, which predominates in the late irreparable injury
and accentuates the cellular depletion of the parenchyma. The complicating factor in the vulnerability of
children to late radiation damage is that the tissues (organs) comprising the mosaic of the human body
develop and mature at different rates and temporal sequences, gaining mass through cell hypertrophy,
proliferation, and stromal development. Since intrinsic radiation sensitivity and vulnerability to radiation-
induced normal tissue damage is related to cellular activity and level of maturation, these phenomena
must be appreciated in order to understand radiation injury in children. Technologic advances in radiation
therapy, such as intensity modulation and proton therapy, will be described. These themes will be
explored in a discussion of the spectrum of late radiation injuries that occur in children treated for cancer.
*1. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood
cancer. N Engl J Med 2006; 355:1572-1582. *2. Armstrong GT, Liu Q, Yasui Y, et al. Late mortality among
5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study. J Clin Oncol
2009:27:2328-2338. *3. Mertens AC, Liu Q, Neglia JP, et al. Cause-specific late mortality among 5-year
survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 2008:100):1368-
1379.
(S1704) Radiation-related Second Primary Solid Cancers among Childhood Cancer Survivors: Radiation
Dose-response and Effect Modification. Peter Inskip, National Institutes of Health, Bethesda, MD
The majority of childhood cancer patients now achieve long-term survival, but the aggressive treatments
often put them at risk of adverse health outcomes years later. Second primary cancers are among the
most serious and psychologically traumatic of late effects. The Childhood Cancer Survivor Study (CCSS) is
a unique resource for the study of second solid cancers, including more than 14,000 five-year survivors of
childhood cancer diagnosed between 1970 and 1986 with long-term follow-up. Investigators from NCI
and the CCSS have collaborated in a series of site-specific second cancer analyses, including central
nervous system, breast, thyroid gland, bone and soft tissue, salivary glands and skin. These studies, which
include organ-specific radiation dosimetry for individuals, have demonstrated the central role of radiation
therapy in the occurrence of new solid cancers. Linear dose-response relationships over wide ranges of
radiation dose were seen for all cancer sites except the thyroid gland. The steepest slopes occurred in
sarcoma, meningioma and skin cancer, with glioma and cancers of the breast and salivary glands forming
a second group. Thyroid cancer risk increased up to 15-20 Gy and then decreased, most likely due to cell-
sterilizing effects of high-dose radiation. We also identified a risk of thyroid cancer associated with
chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses
of radiation to the thyroid. Excess risk of radiation-related breast cancer was sharply reduced among
women who received ≥ 5 Gy to the ovaries, most likely due to reduced exposure of radiation-damaged
breast cells to the stimulating effects of ovarian hormones. The association with dose for glioma was
significant only for radiation exposures occurring prior to age five, suggesting that radio-sensitivity is
greatest when the brain is developing. Results suggest the effect of high-dose irradiation is consistent with
a linear dose-response for most organs but also reveal important organ- and host-specific differences in
sensitivity. The combination of long-term follow-up and organ-specific radiation dosimetry allows for
69 | P a g e
dosage rate, overall treatment time, machine energy, treatment volume, and dosage distribution.
Radiation damage is produced by some combination of parenchymal cell loss and injury to the underlying
vasculature. Initial tissue recovery results mainly from parenchymal cell repopulation. The progressive
component of damage is the arteriolar-capillary fibrosis, which predominates in the late irreparable injury
and accentuates the cellular depletion of the parenchyma. The complicating factor in the vulnerability of
children to late radiation damage is that the tissues (organs) comprising the mosaic of the human body
develop and mature at different rates and temporal sequences, gaining mass through cell hypertrophy,
proliferation, and stromal development. Since intrinsic radiation sensitivity and vulnerability to radiation-
induced normal tissue damage is related to cellular activity and level of maturation, these phenomena
must be appreciated in order to understand radiation injury in children. Technologic advances in radiation
therapy, such as intensity modulation and proton therapy, will be described. These themes will be
explored in a discussion of the spectrum of late radiation injuries that occur in children treated for cancer.
*1. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood
cancer. N Engl J Med 2006; 355:1572-1582. *2. Armstrong GT, Liu Q, Yasui Y, et al. Late mortality among
5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study. J Clin Oncol
2009:27:2328-2338. *3. Mertens AC, Liu Q, Neglia JP, et al. Cause-specific late mortality among 5-year
survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 2008:100):1368-
1379.
(S1704) Radiation-related Second Primary Solid Cancers among Childhood Cancer Survivors: Radiation
Dose-response and Effect Modification. Peter Inskip, National Institutes of Health, Bethesda, MD
The majority of childhood cancer patients now achieve long-term survival, but the aggressive treatments
often put them at risk of adverse health outcomes years later. Second primary cancers are among the
most serious and psychologically traumatic of late effects. The Childhood Cancer Survivor Study (CCSS) is
a unique resource for the study of second solid cancers, including more than 14,000 five-year survivors of
childhood cancer diagnosed between 1970 and 1986 with long-term follow-up. Investigators from NCI
and the CCSS have collaborated in a series of site-specific second cancer analyses, including central
nervous system, breast, thyroid gland, bone and soft tissue, salivary glands and skin. These studies, which
include organ-specific radiation dosimetry for individuals, have demonstrated the central role of radiation
therapy in the occurrence of new solid cancers. Linear dose-response relationships over wide ranges of
radiation dose were seen for all cancer sites except the thyroid gland. The steepest slopes occurred in
sarcoma, meningioma and skin cancer, with glioma and cancers of the breast and salivary glands forming
a second group. Thyroid cancer risk increased up to 15-20 Gy and then decreased, most likely due to cell-
sterilizing effects of high-dose radiation. We also identified a risk of thyroid cancer associated with
chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses
of radiation to the thyroid. Excess risk of radiation-related breast cancer was sharply reduced among
women who received ≥ 5 Gy to the ovaries, most likely due to reduced exposure of radiation-damaged
breast cells to the stimulating effects of ovarian hormones. The association with dose for glioma was
significant only for radiation exposures occurring prior to age five, suggesting that radio-sensitivity is
greatest when the brain is developing. Results suggest the effect of high-dose irradiation is consistent with
a linear dose-response for most organs but also reveal important organ- and host-specific differences in
sensitivity. The combination of long-term follow-up and organ-specific radiation dosimetry allows for
69 | P a g e
