Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study

Henderson, Tara O.; Whitton, John; Stovall, Marilyn; Mertens, Ann C.; Mitby, Pauline; Friedman, Debra L.; Strong, Louise C.; Hammond, Sue; Neglia, Joseph P.; Meadows, Anna T.; Robison, Leslie L.; Diller, Lisa

doi:10.1093/jnci/djk052

Cited by 177 publications

(147 citation statements)

References 28 publications

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“…For the majority of these sites, risks were greater among those who survived 5 or more years after initial radiotherapy, in keeping with the latent period typical for radiationrelated solid cancers. 22 These findings are consistent with prior studies that evaluated the risks of radiation-induced solid cancers among cancer survivors [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] as well as atomic bomb survivors and other radiation-exposed populations. 22,39,40 Our finding of a nearly 6-fold increased risk for radiation-associated breast cancer after HCT confirms a recent report linking breast cancer excesses with young age at transplantation (younger than 18 years) and use of TBI, with the risk increasing sharply among those followed for 10 or more years.…”

Section: Discussionsupporting

confidence: 87%

Solid cancers after allogeneic hematopoietic cell transplantation

Rizzo

Curtis

Socié

et al. 2009

Blood

425

472

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Transplant recipients have been reported to have an increased risk of solid cancers but most studies are small and have limited ability to evaluate the interaction of host, disease, and treatment-related factors. In the largest study to date to evaluate risk factors for solid cancers, we studied a multi-institutional cohort of 28 874 allogeneic transplant recipients with 189 solid malignancies. Overall, patients developed new solid cancers at twice the rate expected based on general population rates (observed-to-expected ratio 2.1; 95% confidence interval 1.8-2.5), with the risk increasing over time (P trend < .001); the risk reached 3-fold among patients followed for 15 years or more after transplantation. New findings showed that the risk of developing a non-squamous cell carcinoma (non-SCC) following conditioning radiation was highly dependent on age at exposure. Among patients irradiated at ages under 30 years, the relative risk of non-SCC was 9 times that of nonirradiated patients, while the comparable risk for older patients was 1.1 (P interaction < .01). Chronic graft-versus-host disease and male sex were the main determinants for risk of SCC. These data indicate that allogeneic transplant survivors, particularly those irradiated at young ages, face increased risks of solid cancers, supporting strategies to promote lifelong surveillance among these patients. (Blood. 2009; 113:1175-1183)

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Section: Discussionsupporting

confidence: 87%

Solid cancers after allogeneic hematopoietic cell transplantation

Rizzo

Curtis

Socié

et al. 2009

Blood

425

472

View full text Add to dashboard Cite

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“…8,[36][37][38][39][40][41][42][43][44][45][46] This information is essential to guide modification of primary cancer therapies to decrease the risk of developing subsequent cancers in newly diagnosed patients. Survivor groups established to be at high risk for carcinogenesis can then be targeted for preventive strategies or interventions that facilitate early detection of subsequent cancers.…”

Section: Subsequent Neoplasmsmentioning

confidence: 99%

“…38 Previous studies had primarily focused on the role of radiation in the development of sarcoma, whereas associations between secondary sarcoma and chemotherapy-age at treatment and family history of cancer-had not been as well studied.…”

Section: Sarcomamentioning

confidence: 99%

High-Risk Populations Identified in Childhood Cancer Survivor Study Investigations: Implications for Risk-Based Surveillance

Hudson

Mulrooney

Bowers

et al. 2009

JCO

127

101

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A B S T R A C TChildhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.

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“…One long term side effect of concern particularly for pediatric patients is the development of a second cancer. 1 Dose-response relationships for cancer risk prediction are usually obtained by analyzing retrospective cohort studies. At present, the largest amount of data available comes from the survivors of the atomic bomb incident in Japan.…”

Section: Introductionmentioning

confidence: 99%

Assessment of uncertainties in radiation‐induced cancer risk predictions at clinically relevant doses

2015

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Purpose: Theoretical dose-response models offer the possibility to assess second cancer induction risks after external beam therapy. The parameters used in these models are determined with limited data from epidemiological studies. Risk estimations are thus associated with considerable uncertainties. This study aims at illustrating uncertainties when predicting the risk for organ-specific second cancers in the primary radiation field illustrated by choosing selected treatment plans for brain cancer patients. Methods: A widely used risk model was considered in this study. The uncertainties of the model parameters were estimated with reported data of second cancer incidences for various organs. Standard error propagation was then subsequently applied to assess the uncertainty in the risk model. Next, second cancer risks of five pediatric patients treated for cancer in the head and neck regions were calculated. For each case, treatment plans for proton and photon therapy were designed to estimate the uncertainties (a) in the lifetime attributable risk (LAR) for a given treatment modality and (b) when comparing risks of two different treatment modalities. Results: Uncertainties in excess of 100% of the risk were found for almost all organs considered. When applied to treatment plans, the calculated LAR values have uncertainties of the same magnitude. A comparison between cancer risks of different treatment modalities, however, does allow statistically significant conclusions. In the studied cases, the patient averaged LAR ratio of proton and photon treatments was 0.35, 0.56, and 0.59 for brain carcinoma, brain sarcoma, and bone sarcoma, respectively. Their corresponding uncertainties were estimated to be potentially below 5%, depending on uncertainties in dosimetry. Conclusions: The uncertainty in the dose-response curve in cancer risk models makes it currently impractical to predict the risk for an individual external beam treatment. On the other hand, the ratio of absolute risks between two modalities is less sensitive to the uncertainties in the risk model and can provide statistically significant estimates. C 2015 American Association of Physicists in Medicine.

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Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study

Abstract: Childhood cancer survivors appear to be at increased risk for secondary sarcomas compared with general population rates.

Cited by 177 publications

References 28 publications

Solid cancers after allogeneic hematopoietic cell transplantation

Solid cancers after allogeneic hematopoietic cell transplantation

High-Risk Populations Identified in Childhood Cancer Survivor Study Investigations: Implications for Risk-Based Surveillance

Assessment of uncertainties in radiation‐induced cancer risk predictions at clinically relevant doses

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