Secondary Malignant Neoplasms after Osteosarcoma: Early Onset and Cumulative Alkylating Agent Dose Dependency

Kim, Seung Hyun; Shin, Kyoo Ho; Seok, Sang Ok; Cho, Yong Jin; Noh, Jae Kyoung; Yang, Woo Ick

doi:10.1245/s10434-014-4070-2

Cited by 7 publications

(7 citation statements)

References 28 publications

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“…The Childhood Cancer Survivor Study (CCSS) and other cohorts of childhood cancer survivors have reported extensively on the incidence of and risk factors for subsequent neoplasms . Therapeutic radiation has been strongly associated with development of subsequent neoplasms; however, dose-response relationships have also been identified for specific chemotherapeutic agents, including alkylating agents and epipodophyllotoxins . With this knowledge, childhood cancer treatment has been modified over time with the hope of reducing subsequent neoplasm risk, while maintaining or improving 5-year survival …”

Section: Introductionmentioning

confidence: 99%

Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015

Turcotte

Liu

Yasui

et al. 2017

JAMA

193

196

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IMPORTANCE Cancer treatments are associated with subsequent neoplasms in survivors of childhood cancer. It is unknown whether temporal changes in therapy are associated with changes in subsequent neoplasm risk.OBJECTIVE To quantify the association between temporal changes in treatment dosing and subsequent neoplasm risk.DESIGN, SETTING, AND PARTICIPANTS Retrospective, multicenter cohort study of 5-year cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970-1999, with follow-up through December 2015.EXPOSURES Radiation and chemotherapy dose changes over time.MAIN OUTCOMES AND MEASURES Subsequent neoplasm 15-year cumulative incidence, cumulative burden, and standardized incidence ratios for subsequent malignancies, compared by treatment decade. Multivariable models assessed relative rates (RRs) of subsequent neoplasms by 5-year increments, adjusting for demographic and clinical characteristics. Mediation analyses assessed whether changes in rates of subsequent neoplasms over time were mediated by treatment variable modifications. RESULTS Among 23 603 survivors of childhood cancer (mean age at diagnosis, 7.7 years; 46% female) the most common initial diagnoses were acute lymphoblastic leukemia, Hodgkin lymphoma, and astrocytoma. During a mean follow-up of 20.5 years (374 638 person-years at risk), 1639 survivors experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 nonmelanoma skin cancers. The most common subsequent malignancies were breast and thyroid cancers. Proportions of individuals receiving radiation decreased (77% for 1970s vs 33% for 1990s), as did median dose (30 Gy [interquartile range, 24-44] for 1970s vs 26 Gy [interquartile range, 18-45] for 1990s). Fifteen-year cumulative incidence of subsequent malignancies decreased by decade of diagnosis (2.1% [95% CI, 1.7%-2.4%] for 1970s, 1.7% [95% CI, 1.5%-2.0%] for 1980s, 1.3% [95% CI, 1.1%-1.5%] for 1990s). Reference absolute rates per 1000 person-years were 1.12 (95% CI, 0.84-1.57) for subsequent malignancies, 0.16 (95% CI, 0.06-0.41) for meningiomas, and 1.71 (95% CI, 0.88-3.33) for nonmelanoma skin cancers for survivors with reference characteristics (no chemotherapy, splenectomy, or radiation therapy; male; attained age 28 years). Standardized incidence ratios declined for subsequent malignancies over treatment decades, with advancing attained age. Relative rates declined with each 5-year increment for subsequent malignancies (RR, 0.87 [95% CI, 0.82-0.93]; P < .001), meningiomas (RR, 0.85 [95% CI, 0.75-0.97]; P = .03), and nonmelanoma skin cancers (RR, 0.75 [95% CI, 0.67-0.84]; P < .001). Radiation dose changes were associated with reduced risk for subsequent malignancies, meningiomas, and nonmelanoma skin cancers.CONCLUSIONS AND RELEVANCE Among survivors of childhood cancer, the risk of subsequent malignancies at 15 years after initial cancer diagnosis remained increased for those diagnosed in the 1990s, although the risk was lower compar...

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Section: Introductionmentioning

confidence: 99%

Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015

Turcotte

Liu

Yasui

et al. 2017

JAMA

193

196

View full text Add to dashboard Cite

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“…Therefore, a long follow-up period is needed after primary treatment for OS to detect both SPMs as well as recurrence, metastasis, or multiple OS ( 9 , 24 , 35 , 36 ). SPMs after OS can be fatal ( 6 , 7 ), and together with metastasis, chemotherapy response, tumor characteristics, patient characteristics, surgical margins, and toxicity, SPMs are an important prognostic factor ( 37 ). Indeed, the prognosis is poor once SPMs occur ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Triple primary malignancies of surface osteosarcoma of jaw, myelodysplastic syndrome and colorectal cancer as a second primary cancer detected by PET2‑[18F]‑fluoro‑2‑deoxy‑D‑glucose positron emission tomography: A case report

et al. 2018

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Second primary malignancy (SPM) is a severe issue for cancer survivors, particularly for osteosarcoma (OS) survivors. To date, the associations between subsequent SPM and OS have been well reported. Hematogenic and solid malignancies tend to occur following OS treatment. Reportedly, 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is mainly used in OS patients for initial cancer staging, to evaluate the response of neoadjuvant chemotherapy, and when recurrence or metastasis is clinically suspected. The present case report describes a 70-year-old man diagnosed with three primary malignancies: jaw OS, myelodysplastic syndrome and colorectal adenocarcinoma. To the best of our knowledge, this combination of malignancies has not been reported previously. Until now, there is no specific protocol of postoperative FDG-PET for OS patients. Few studies have described OS follow-up methods; therefore, there is no consensus on proper follow-up methods. In the present case report, the colorectal early-stage SPM was observed, without any symptoms, by FDG-PET/computed tomography. To avoid overlooking solid SPMs, it is suggested that FDG-PET should be performed in the long-term follow-up of OS patients.

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“…In a retrospective study by Kim et al, a high cumulative alkylating agent dose was found to be an independent risk factor for second malignant neoplasms and its early development after osteosarcoma treatment [ 10 ]. In our patient, the cumulative dose of ifosfamide used was 21.6 gm/m2.…”

Section: Discussionmentioning

confidence: 99%

Ifosfamide-Induced Malignancy of Ureter and Bladder

Sannu

Mathews

et al. 2017

Cureus

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Secondary Malignant Neoplasms after Osteosarcoma: Early Onset and Cumulative Alkylating Agent Dose Dependency

Abstract: High cumulative AAS is an independent risk factor for SMN and its early-onset development after osteosarcoma.

Cited by 7 publications

References 28 publications

Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015

Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015

Triple primary malignancies of surface osteosarcoma of jaw, myelodysplastic syndrome and colorectal cancer as a second primary cancer detected by PET2‑[18F]‑fluoro‑2‑deoxy‑D‑glucose positron emission tomography: A case report

Ifosfamide-Induced Malignancy of Ureter and Bladder

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