Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood

Menu-Branthomme, Axelle; Rubino, Carole; Shamsaldin, Akhtar; Hawkins, Michael M.; Grimaud, Emmanuel; Dondon, Marie-Gabrielle; Hardiman, Claire; Vassal, Gilles; Campbell, Sarah; Panis, X.; Daly-Schveitzer, N.; Lagrange, Jean‐Léon; Zucker, Jean‐Michel; Chavaudra, J.; Hartman, O; Vathaire, Florent de

doi:10.1002/(sici)1097-0215(19980729)77:3<370::aid-ijc11>3.0.co;2-c

Cited by 155 publications

(83 citation statements)

References 17 publications

(18 reference statements)

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“…Second bone cancers have been evaluated after childhood cancer and cervical cancer (21–24). In the studies of childhood cancer, there was clear evidence of increasing risks with increasing doses and no evidence of a downturn even at doses of >60 Gy (21,23,24) (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

González

Gilbert

Curtis

et al. 2013

International Journal of Radiation Oncology*Biology*Physics

228

154

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Rapid innovation in radiotherapy techniques has resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, since direct observation of the late-effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1–5 gray (Gy)). In particular, there is uncertainty about the shape of the dose-response curve at high doses, and the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5Gy) from radiotherapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3,434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was non-linear in the direction of a down-turn in risk, even at organ doses of ≥60Gy. Thyroid cancer was the only exception with evidence of a downturn after 20Gy. Generally the excess relative risk per Gy, taking account of age and sex, was 5–10 times lower than the risk from acute exposures of <2Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to second cancer. The results from our review provide insights into radiation carcinogenesis from fractionated high-dose exposures, and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiotherapy techniques.

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Section: Resultsmentioning

confidence: 99%

Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

González

Gilbert

Curtis

et al. 2013

International Journal of Radiation Oncology*Biology*Physics

228

154

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“…Radiation too has been implicated in causation 12. The risk of developing postradiation osteosarcoma correlates with radiation dose and use of electrophilic chemotherapeutic agents 131415. An etiological relationship has not been proven in prosthesis and metal hardware associated osteosarcomas 16…”

Section: Introductionmentioning

confidence: 99%

Classification, imaging, biopsy and staging of osteosarcoma

Kundu

2014

IJOO

115

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Osteosarcoma is the most common primary osseous malignancy excluding malignant neoplasms of marrow origin (myeloma, lymphoma and leukemia) and accounts for approximately 20% of bone cancers. It predominantly affects patients younger than 20 years and mainly occurs in the long bones of the extremities, the most common being the metaphyseal area around the knee. These are classified as primary (central or surface) and secondary osteosarcomas arising in preexisting conditions. The conventional plain radiograph is the best for probable diagnosis as it describes features like sun burst appearance, Codman's triangle, new bone formation in soft tissues along with permeative pattern of destruction of the bone and other characteristics for specific subtypes of osteosarcomas. X-ray chest can detect metastasis in the lungs, but computerized tomography (CT) scan of the thorax is more helpful. Magnetic resonance imaging (MRI) of the lesion delineates its extent into the soft tissues, the medullary canal, the joint, skip lesions and the proximity of the tumor to the neurovascular structures. Tc99 bone scan detects the osseous metastases. Positron Emission Tomography (PET) is used for metastatic workup and/or local recurrence after resection. The role of biochemical markers like alkaline phosphatase and lactate dehydrogenase is pertinent for prognosis and treatment response. The biopsy confirms the diagnosis and reveals the grade of the tumor. Enneking system for staging malignant musculoskeletal tumors and American Joint Committee on Cancer (AJCC) staging systems are most commonly used for extremity sarcomas.

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“…Studies of childhood post-irradiation sarcomas reveal that the most frequent second solid cancer occurring in children treated with radiation therapy is osteosarcoma (30). In adult breast cancer patients treated with fractionated radio-therapy (2 Gy/day, 5 weekly fractions) with median doses of 50-55 Gy, the most common tumor was angiosarcoma, followed by undifferentiated sarcoma and osteosarcoma (31).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly in humans, studies of childhood post-irradiation sarcomas provide clear evidence of increased risks with no evidence of a decrease in slope with doses ≥ 60 Gy (30, 32, 33). For breast cancer patients in adulthood, increased risk of post-irradiation sarcomas are also associated with increasing dose (35).…”

Section: Discussionmentioning

confidence: 99%

Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

Edmondson

Hunter

Weil

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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Purpose To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single dose or clinically relevant, fractioned dose γ-ray radiation. Methods C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gray (Gy) or fractionated doses totaling 40 to 80 Gy delivered at 2 Gy/day fractions, 5 days/week, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days following irradiation and all tumors were characterized histologically. Results A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed following fractionated irradiation (16.4%) in comparison to single dose irradiation (36.1%). Sarcomas were the predominant post-irradiation tumor observed (n = 201) with carcinomas occurring less frequently (n = 9). The proportion of mice developing tumors increased significantly with total dose for both single dose and fractionated schedules and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice following single dose irradiation, however, significant differences in tumor susceptibilities following fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common following fractionated irradiation whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common following single dose irradiation. Conclusions This study investigated the tumorigenic effect of acute large doses in comparison to fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiotherapy. Differences in tumor histotype following single dose or fractionated radiation exposures provides novel in vivo evidence for differences in tumor susceptibility amongst stromal cell populations.

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Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood

Cited by 155 publications

References 17 publications

Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

Classification, imaging, biopsy and staging of osteosarcoma

Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

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