open access: Radiotherapy-Induced Malignancies: Review of Clinical Features, Pathobiology, and Evolving Approaches for Mitigating Risk

 Blogger's Note: please read the full paper for context

open access

One of the most significant effects of radiation therapy on normal tissues is mutagenesis, which is the basis for radiation-induced malignancies. Radiation-induced malignancies are late complications arising after radiotherapy, increasing in frequency among survivors of both pediatric and adult cancers. Genetic backgrounds harboring germline mutations in tumor suppressor genes are recognized risk factors. Some success has been found with using genome wide association studies to identify germline polymorphisms associated with susceptibility. The insights generated by genetics, epidemiology, and the development of experimental models are defining potential strategies to offer to individuals at risk for radiation-induced malignancies. Concurrent technological efforts are developing novel radiotherapy delivery to reduce irradiation of normal tissues, and thereby, to mitigate the risk of radiation-induced malignancies. The goal of this review is to discuss epidemiologic, modeling, and radiotherapy delivery data, where these lines of research intersect and their potential impact on patient care.

Radiation-Induced Tumors:

Atomic Bomb Survivors

Radiation-Induced Tumors after Radiotherapy for Non-Oncologic Diseases

Second Malignant Neoplasms - Second malignant neoplasms (SMNs) are late complications arising after exposure to genotoxic therapies, which include radiotherapy and some chemotherapeutic agents...see Table 1

Radiotherapy for Leukemia

Thoracic Irradiation

(The risk of breast cancer is influenced by hormone status, as women with histories of ovarian irradiation of 5 Gy or more had reduced risk of breast cancer compared to women who did not (Travis et al., 2003). Consistent with the hormone-dependence, radiation-induced breast cancers were significantly less likely to develop in women who were menopausal before the age of 40 (Travis et al., 2003). )

Head and Neck Irradiation

Genitourinary Irradiation

Hematologic Malignancies as SMNs

 

Modifiers of Radiation-Induced Tumorigenesis:

Genetic Background 

( ...."In general, individuals with tumor predisposition syndromes should be considered at risk for SMNs after radiation.)

Influence of Age

Pathogenesis of Radiation-Induced Tumors

Mathematical Models of Radiation-Induced Tumorigenesis

Microenvironmental Contributions to Radiation-Induced Tumorigenesis

The Bystander Effect

Clinically Based Animal Models of SMNs

Radiotherapy Techniques

Field Size

Consideration of Radiotherapy Treatment Modality

Intensity Modulated Radiation Therapy

Proton Therapy

Clinical Comparison of Modalities

 

Conclusion

Radiotherapy continues to be a critical component of oncologic care. As cancer survival improves, the late effects of radiotherapy can impact long-term patient health. The most significant and life-threatening of late effects is the development of an SMN. A review of the literature demonstrates that radiation-induced tumors develop after relatively long latencies of often several years, but that this risk often persists for decades without a plateau. Defining the conditions that promote this complication will allow us to develop both treatments and cancer preventive strategies for individuals diagnosed with cancer (Figure 1). Low dose radiation is associated with an increased risk of tumor development in a variety of normal tissues, and susceptibility can be strongly influenced by genetic background and likely additional factors. These data should influence how we evaluate technologies and the care of cancer survivors moving forward..........

 Figure 1. Schematic of secondary malignant neoplasm (SMN) development.

Blogger's Note: aside from the excerpt noted under Thoracic, the only reference material to ovarian is:

(open access - 1996) Travis, L. B., Curtis, R. E., Boice, J. D. Jr., Platz, C. E., Hankey, B. F., and Fraumeni, J. F. Jr. (1996). Second malignant neoplasms among long-term survivors of ovarian cancer. Cancer Res. 56, 1564–1570.