Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models?

Abstract

In the era of modern radiation therapy, the compromise between the reductions in deterministic radiation-induced toxicities through highly conformal devices may be impacting the stochastic risk of second malignancies. We reviewed the clinical literature and evolving theoretical models evaluating the impact of intensity-modulated radiation therapy (IMRT) on the risk of second cancers, as a consequence of the increase in volumes of normal tissues receiving low doses. The risk increase (if any) is not as high as theoretical models have predicted in adults. Moreover, the increase in out-of-field radiation doses with IMRT could be counterbalanced by the decrease in volumes receiving high doses. Clinical studies with short follow-up have not corroborated the hypothesis that IMRT would drastically increase the incidence of second cancers. In children, the risk of radiation-induced carcinogenesis increases from low doses and consequently the relative risk of second cancers after IMRT could be higher than in adults, justifying current developments of proton therapy with priority given to this population. Although only longer follow-up will allow a true assessment of the real impact of these modern techniques on radiation-induced carcinogenesis, a comprehensive risk-adapted strategy will help minimize the probability of second cancers.

Brachytherapy: An overview for clinicians

“…Second cancers are among the most feared complications after radiotherapy in childhood. Although the specific impact of modern technologies is still under investigation, theoretical models suggest that IMRT may increase the risk of second malignancies as a consequence of the increase in the volume of normal tissues receiving low doses . Therefore, it is very important to keep irradiated volumes as low as possible to minimize the risk of second cancers and, in this context, brachytherapy has been proposed with high efficacy and acceptable morbidity by expert teams in pediatric patients as part of a multimodal conservative strategy for children with bladder and/or prostate rhabdomyosarcoma.…”

Suppression of Sclerostin Alleviates Radiation-Induced Bone Loss by Protecting Bone-Forming Cells and Their Progenitors Through Distinct Mechanisms

“…The aim of radiotherapy is to target its destructive effects on tumor cells while limiting its damage to nearby healthy tissues. This has been improved greatly by computer‐assisted treatment planning and innovations in technologies, such as proton and intensity‐modified radiotherapy . However, loss of bone density and an elevated risk of fracture remain problematic late effects of radiotherapy .…”

“…This has been improved greatly by computer-assisted treatment planning and innovations in technologies, such as proton and intensity-modified radiotherapy. (3) However, loss of bone density and an elevated risk of fracture remain problematic late effects of radiotherapy. (4) With the ever-increasing survival rate and longevity of cancer patients, understanding the mechanism of radiation-induced bone loss and identifying preventive or curative treatments are of greater clinical significance than ever before.…”

Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation‐induced osteoporosis

“…As an effective treatment that damages tumor DNA and induces tumor cell death, radiotherapy has been successfully used in patients with cancer, alone or in conjunction with chemotherapy, for many decades (1). Clinical radiotherapy is undergoing constant refinement, and current technologies are increasingly focused on mitigating its harmful effect on the neighboring tissues (2). Nonetheless, the deleterious effect of ionizing radiation on bone adjacent to tumors is a well-recognized late side effect of radiotherapy that frequently leads to osteoradionecrosis and osteoporotic-or stress-induced fractures (3,4).…”