Second Malignant Neoplasm
Radiotherapy (RT) related:
RT induces solid tumors such as sarcomas
- Within or at the edge of the RT treatment field
Different tissues show different sensitivities
- Breast and thyroid especially sensitive
Latency period of RT associated solid tumors is usually much longer than for secondary leukemia, typically 10 years or more.
Lower relative risks for solid SMNs as compared with leukemias, but account for the largest absolute burden of second cancers.
- RT for retinoblastoma and Ewing sarcoma associated with an increased risk of secondary osteogenic sarcoma
- Higher risk of RT induced bone tumors and sarcomas with higher dose of RT
- Within RT field
- Generally about 10 years or more later
- Don’t respond especially well to therapy
Hodgkin Lymphoma (HL) and Breast cancer:
Breast cancer is the most common solid tumor among female survivors of HL11. 12.
This increased risk is largely due to moderately high-dose mediastinal RT with significant scatter to adjacent (breast) tissues.
Risk inversely correlated with age at treatment (increased sensitivity for young women, especially if treated during puberty).
Analytic, international investigation13 of HL patients estimating long-term risk according to RT dose to the area in the breast where cancer was later diagnosed (took into account chemotherapy- or RT-related ovarian damage).
Population-based cancer registries in Iowa, Ontario, Denmark, Finland, the Netherlands, and Sweden identified a cohort of 3,817 1-year female survivors of Hodgkin lymphoma diagnosed at age 30 (1965-1994).
105 cases of breast cancer found and matched to a stratified, random sample of women with HL who did not develop breast cancer
Statistical analysis to:
- Estimate the relative risk of breast cancer in terms of RT dose to site of breast cancer and to the ovaries
- Cumulative dose of alkylating agent chemotherapy, and other risk factors.
- RT dose to the breast 4 Gy led to significantly increased 3.2-fold risk of breast cancer compared with women who received lower breast doses without alkylating agents.
- Risk of breast cancer increased with increasing RT dose to reach 8-fold at >40 Gy (P trend for dose < 0.001).
- Excess RT-related breast cancers occurred for >25 years after exposure (effect of RT dose still evident.
- RT combined with alkylating agents was associated with a non-significant 1.4-fold risk of breast cancer.
- Treatment with alkylating agent chemotherapy alone was associated with a 40% reduction in risk. The risk of breast cancer decreased sharply with an increasing number of cycles of alkylating agent chemotherapy.
- There was a 50% decrease in breast cancer risk after a dose of 5 Gy to the ovaries.
- Menopause before age 40 years was associated with a significant decrease in breast cancer risk compared with women who remained premenopausal.
Smaller RT fields and lower doses now used to treat HL, should eventually result in lower risks of breast cancer.
Estimates of the cumulative absolute risk of breast cancer among young women treated for Hodgkin lymphoma at age 30 years have been inconsistent, varying from 4.2% to 34% at 20 to 25 years after therapy.
Most estimates do not taken into account the influence of alkylating agent therapy, which can lower breast cancer risk or the effect of competing causes of mortality.
David Rakoff (author, humorist and actor) wrote about waiting to hear the results of his medical tests. He was originally treated for Hodgkin lymphoma and developed a secondary sarcoma in the region of his left clavicle (presumably related to his mantle field radiation therapy).
Sadly he died of his secondary malignancy