Subsequent Neoplasms

Subsequent neoplasms comprise two distinct groups:[56,57]

Subsequent neoplasms comprise two distinct groups:[56,57]

Myelodysplasia and acute myeloid leukemia (AML) related to chemotherapy. Subsequent hematological malignancy is related to the use of alkylating agents, anthracyclines, and etoposide and exhibit a brief latency period (<10 years from the primary cancer).[58] This excess risk is largely related to cases of myelodysplasia and subsequent AML. A single-study experience suggests that there could be an increase in malignancies when multiple topoisomerase inhibitors are administered in close proximity.[44] Clinical trials using dexrazoxane in childhood leukemia have not observed an excess risk of subsequent neoplasms.[44,59,60]Chemotherapy-related myelodysplasia and AML are less prevalent after contemporary therapy because of the restriction of cumulative alkylating agent doses.[61,62]Among 1,711 intermediate-risk Hodgkin lymphoma survivors treated with response-adapted therapy in the COG AHOD0031 (NCT00025259) trial (median follow-up, 7.3 years), the 10-year cumulative incidence of subsequent malignancy was 1.3%, and the cumulative incidence of secondary myelodysplastic syndrome or AML was 0.2%. Of the three cases of secondary AML, the median time to onset was 2 years (range, 1.8–2.7 years).[63]

Subsequent neoplasms comprise two distinct groups:[56,57]

Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

The absolute excess risk of breast cancer ranges from 18.6 to 79 per 10,000 person-years, and the cumulative incidence ranges from 12% to 26%, with onset 25 to 30 years after radiation exposure.[51,65-67]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

High risk of breast cancer has been found to increase as early as 8 years after radiation exposure, is rare before age 25 years, and continues to increase with time from exposure. Importantly, breast cancer in female childhood cancer survivors typically develops at least 25 years earlier than in the general population and often years before the ages recommended for population-based screening.[51]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

The cumulative incidence of breast cancer by age 40 to 45 years ranges from 13% to 20%, compared with 1% for women in the general population.[51,65,67,68] This risk is similar to that observed for women with a BRCA gene variant, for whom the cumulative incidence of breast cancer ranges from 10% to 19% by age 40 years.[69]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

The risk of breast cancer in female survivors of Hodgkin lymphoma is directly related to the dose of radiation therapy received over a range from 4 Gy to 40 Gy.[70] Female patients treated with both radiation therapy and alkylating agent chemotherapy have a lower RR of developing breast cancer than women receiving radiation therapy alone.[52,71]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

CCSS investigators also demonstrated that breast cancer risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries.[72] The protective effect of alkylating chemotherapy and ovarian radiation is believed to be mediated through induction of premature menopause, suggesting that hormone stimulation contributes to the development of radiation-induced breast cancer.[73]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

Several cohort studies have demonstrated a dose-related increased risk of breast cancer among female survivors of childhood, adolescent, and young adult cancer treated with anthracycline chemotherapy.[74-77]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

St. Jude Lifetime Cohort investigators observed that treatment with anthracycline doses of 250 mg/m2 or higher was associated with increased breast cancer risk in survivors who did not have pathogenic (or likely pathogenic) cancer-predisposing variants and who did not receive chest radiation therapy.[77]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

CCSS investigators reported an additive interaction between anthracyclines and chest radiation therapy, as the risk associated with this combination was higher than the sum of the individual risks.[75]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

Evidence for risk of breast cancer after treatment with higher doses of alkylating agents without chest radiation therapy has been conflicting, with one study reporting an increased risk and others not observing this effect.[74,75,78]

Subsequent neoplasms comprise two distinct groups:[56,57] › Solid neoplasms that are predominately related to radiation. Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,64]; [55][Level of evidence C1] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. For more information about subsequent thyroid neoplasms, see the Thyroid Abnormalities section.Breast cancer is the most common therapy-related, solid, subsequent neoplasm after treatment of Hodgkin lymphoma:Breast cancer risk after radiation therapy:Breast cancer risk after chemotherapy (includes survivors of Hodgkin lymphoma and other childhood, adolescent, and young adult malignancies):

The evidence is inconsistent about risks and dose thresholds for breast cancer after treatment with chemotherapy in women who did not receive chest radiation. Shared decision-making is recommended for planning breast cancer surveillance.[79]