Bone and soft tissue tumors

Radiation therapy is associated with a linear dose-response relationship.[75,76]

In a PENTEC investigation on subsequent malignancies, the estimated pooled ERR/Gy for subsequent sarcomas was 0.045. There was a possible biphasic dose response, with higher rates of relapse and subsequent sarcomas above 55 Gy. After 20 Gy and anthracyclines, the absolute excess risk is predicted to be 0.24% at 50 years and 0.86% at 75 years. The median latency time to the development of sarcomas was 11 years (range, 4–23 years).[61]

After adjustment for radiation therapy, treatment with alkylating agents [13,61] and anthracyclines [77] have both been linked to sarcoma, with the risk increasing with cumulative drug exposure.[77]

Soft tissue sarcomas can be of various histological subtypes, including nonrhabdomyosarcoma soft tissue sarcomas, rhabdomyosarcoma, malignant peripheral nerve sheath tumors, Ewing/primitive neuroectodermal tumors, and other rare tumor types.

A nested case-control study included 228 cases and 228 matched controls within a cohort of 69,460 5-year survivors of childhood cancer. The study investigated the risks of subsequent primary bone cancer by different levels of cumulative radiation exposure and dose-response relationships according to different specific types of chemotherapy.[78]

A nested case-control study included 228 cases and 228 matched controls within a cohort of 69,460 5-year survivors of childhood cancer. The study investigated the risks of subsequent primary bone cancer by different levels of cumulative radiation exposure and dose-response relationships according to different specific types of chemotherapy.[78]

Compared with unexposed bone tissue, the OR associated with bone tissue exposed to 1 to 4 Gy was 4.8-fold (95% CI, 1.2–19.6). The OR associated with bone tissue exposed to 5 to 9 Gy was 9.6-fold (95% CI, 2.4–37.4). The OR increased linearly with increasing doses of radiation (Ptrend < .001), up to 78-fold (95% CI, 9.2–669.9) for doses of 40 Gy or higher.

A nested case-control study included 228 cases and 228 matched controls within a cohort of 69,460 5-year survivors of childhood cancer. The study investigated the risks of subsequent primary bone cancer by different levels of cumulative radiation exposure and dose-response relationships according to different specific types of chemotherapy.[78]

For cumulative alkylating agent doses of 10,000 to 19,999 mg/m2 and 20,000 mg/m2 or higher, the radiation-adjusted ORs were 7.1 (95% CI, 2.2–22.8) and 8.3 (95% CI, 2.8–24.4), respectively. There were independent contributions from exposure to procarbazine, ifosfamide, or cyclophosphamide.

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

The risk of subsequent primary bone cancer was 22-fold greater than that of the general population, with an estimated 45-year cumulative incidence of 0.6%, compared with an expected rate of 0.03% in the general population.[71]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

The observed excess numbers of subsequent primary bone cancer declined with both age and years from diagnosis.[71]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

The risk of subsequent soft tissue sarcoma was almost 16-fold higher than the general population, with an estimated 45-year cumulative incidence of 1.4%, compared with an expected rate of 0.1%.[72]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

The median time from diagnosis to occurrence of a soft tissue sarcoma was 19 years.[72]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

The most commonly observed soft tissue sarcomas were leiomyosarcoma, fibromatous neoplasms, and malignant peripheral nerve sheath tumors.[72]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

The SIR for subsequent fibromatous primary sarcomas decreased with increasing years from diagnosis and attained age, whereas the SIR for leiomyosarcoma and malignant peripheral nerve sheath tumors remained consistently high across all years from diagnosis and at all attained ages.[72]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

The absolute excess risks of all sarcoma subtypes were generally low, except for leiomyosarcoma that followed a retinoblastoma diagnosis (absolute excess risks, 52.7 per 10,000 person-years among survivors 45 years or more from diagnosis).[72]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72]

The risk of developing a leiomyosarcoma was 30-fold higher among survivors of childhood cancer, compared with an excess risk of 0.7 for the general population.[72]

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72] › The risk of developing a leiomyosarcoma was 30-fold higher among survivors of childhood cancer, compared with an excess risk of 0.7 for the general population.[72]

Retinoblastoma survivors were at the highest risk (SIR, 342.9), followed by Wilms tumor survivors (SIR, 74.2).

A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:[71,72] › The risk of developing a leiomyosarcoma was 30-fold higher among survivors of childhood cancer, compared with an excess risk of 0.7 for the general population.[72]

90% of leiomyosarcomas observed after a Wilms tumor diagnosis developed within the irradiated tissue.

In a CCSS cohort, an increased risk of subsequent bone or soft tissue sarcoma was associated with radiation therapy, a primary diagnosis of sarcoma, a history of other SNs, and treatment with higher doses of anthracyclines or alkylating agents.[27]

In a CCSS cohort, an increased risk of subsequent bone or soft tissue sarcoma was associated with radiation therapy, a primary diagnosis of sarcoma, a history of other SNs, and treatment with higher doses of anthracyclines or alkylating agents.[27]

The 30-year cumulative incidence of subsequent sarcoma in CCSS participants was 1.08% for survivors who received radiation therapy and 0.5% for survivors who did not receive radiation therapy.

Dose-risk modeling was used to study the risk of bone sarcoma in a retrospective cohort of 4,171 survivors of a childhood solid cancer treated between 1942 and 1986 (median follow-up, 26 years).[75]

Dose-risk modeling was used to study the risk of bone sarcoma in a retrospective cohort of 4,171 survivors of a childhood solid cancer treated between 1942 and 1986 (median follow-up, 26 years).[75]

Results demonstrated that the risk of bone sarcoma increased slightly up to a cumulative organ-absorbed radiation dose of 15 Gy (HR, 8.2; 95% CI, 1.6–42.9) and then rapidly increased for higher radiation doses (HR for 30 Gy or more, 117.9; 95% CI, 36.5–380.6), compared with patients not treated with radiation therapy.

Dose-risk modeling was used to study the risk of bone sarcoma in a retrospective cohort of 4,171 survivors of a childhood solid cancer treated between 1942 and 1986 (median follow-up, 26 years).[75]

The excess RR per Gy in this model was 1.77 (95% CI, 0.62–5.94).

In survivors of bilateral retinoblastoma, the most commonly observed malignant SN is sarcoma, specifically osteosarcoma.[79-81] The contribution of chemotherapy to solid malignancy carcinogenesis was highlighted in a long-term follow-up study of 906 5-year hereditary retinoblastoma survivors who were diagnosed between 1914 and 1996 and observed through 2009.[70]

In survivors of bilateral retinoblastoma, the most commonly observed malignant SN is sarcoma, specifically osteosarcoma.[79-81] The contribution of chemotherapy to solid malignancy carcinogenesis was highlighted in a long-term follow-up study of 906 5-year hereditary retinoblastoma survivors who were diagnosed between 1914 and 1996 and observed through 2009.[70]

Treatment with alkylating agents significantly increased risk of subsequent bone tumors (HR, 1.60; 95% CI, 1.03–2.49) and leiomyosarcoma (HR, 2.67; 95% CI, 1.22–5.85) among members of the cohort.

In survivors of bilateral retinoblastoma, the most commonly observed malignant SN is sarcoma, specifically osteosarcoma.[79-81] The contribution of chemotherapy to solid malignancy carcinogenesis was highlighted in a long-term follow-up study of 906 5-year hereditary retinoblastoma survivors who were diagnosed between 1914 and 1996 and observed through 2009.[70]

Leiomyosarcoma occurrence was more common after treatment with alkylating agent chemotherapy and radiation therapy compared with radiation therapy alone (5.8% vs. 1.6% at age 40 years; P = .01).

The CCSS reported the following on 105 cases and 422 matched controls in a nested case-control study of 14,372 childhood cancer survivors:[77]

The CCSS reported the following on 105 cases and 422 matched controls in a nested case-control study of 14,372 childhood cancer survivors:[77]

Soft tissue sarcomas occurred at a median of 11.8 years (range, 5.3–31.3 years) from original diagnoses.

The CCSS reported the following on 105 cases and 422 matched controls in a nested case-control study of 14,372 childhood cancer survivors:[77]

Any exposure to radiation was associated with increased risk of soft tissue sarcoma (OR, 4.1; 95% CI, 1.8–9.5), which demonstrated a linear dose-response relationship.

The CCSS reported the following on 105 cases and 422 matched controls in a nested case-control study of 14,372 childhood cancer survivors:[77]

Anthracycline exposure was associated with soft tissue sarcoma risk (OR, 3.5; 95% CI, 1.6–7.7), independent of radiation dose.

In a cohort of 952 irradiated survivors of hereditary retinoblastoma diagnosed between 1914 and 2006, CCSS investigators observed that elevated bone and soft tissue sarcoma risks differed by age, location, and sex.[81]

In a cohort of 952 irradiated survivors of hereditary retinoblastoma diagnosed between 1914 and 2006, CCSS investigators observed that elevated bone and soft tissue sarcoma risks differed by age, location, and sex.[81]

Head and neck bone and soft tissue sarcomas were diagnosed beginning in early childhood and continued well into adulthood (60-year cumulative incidence of 6.8% and 9.3%, respectively).

In a cohort of 952 irradiated survivors of hereditary retinoblastoma diagnosed between 1914 and 2006, CCSS investigators observed that elevated bone and soft tissue sarcoma risks differed by age, location, and sex.[81]

Body and extremity bone sarcoma incidence flattened after adolescence (60-year cumulative incidence, 3.5%).

In a cohort of 952 irradiated survivors of hereditary retinoblastoma diagnosed between 1914 and 2006, CCSS investigators observed that elevated bone and soft tissue sarcoma risks differed by age, location, and sex.[81]

Body and extremity soft tissue sarcoma incidence was rare until age 30 years, when incidence rose steeply (60-year cumulative incidence, 6.6%) particularly for females (60-year cumulative incidence, 9.4%).

In a retrospective study of 160 patients with hereditary retinoblastoma who received radiation therapy, no correlation was identified between age (before or after 12 months) at which external-beam radiation therapy was given and development of subsequent malignancy.[73]

In a retrospective study of 160 patients with hereditary retinoblastoma who received radiation therapy, no correlation was identified between age (before or after 12 months) at which external-beam radiation therapy was given and development of subsequent malignancy.[73]

Patients with and without subsequent malignancies did not differ by RB1 variant type. Also, there was no association with variant type and location of SMN, or SMN type and age at diagnosis.

In a retrospective study of 160 patients with hereditary retinoblastoma who received radiation therapy, no correlation was identified between age (before or after 12 months) at which external-beam radiation therapy was given and development of subsequent malignancy.[73]

The study showed that patients who have a low penetrance variant and receive external-beam radiation therapy remain at risk of SMNs and should be cautiously monitored.