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      Intensity-modulated radiation therapy, protons, and the risk of second cancers

      International Journal of Radiation Oncology*Biology*Physics
      Elsevier BV

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          Abstract

          Intensity-modulated radiation therapy (IMRT) allows dose to be concentrated in the tumor volume while sparing normal tissues. However, the downside to IMRT is the potential to increase the number of radiation-induced second cancers. The reasons for this potential are more monitor units and, therefore, a larger total-body dose because of leakage radiation and, because IMRT involves more fields, a bigger volume of normal tissue is exposed to lower radiation doses. Intensity-modulated radiation therapy may double the incidence of solid cancers in long-term survivors. This outcome may be acceptable in older patients if balanced by an improvement in local tumor control and reduced acute toxicity. On the other hand, the incidence of second cancers is much higher in children, so that doubling it may not be acceptable. IMRT represents a special case for children for three reasons. First, children are more sensitive to radiation-induced cancer than are adults. Second, radiation scattered from the treatment volume is more important in the small body of the child. Third, the question of genetic susceptibility arises because many childhood cancers involve a germline mutation. The levels of leakage radiation in current Linacs are not inevitable. Leakage can be reduced but at substantial cost. An alternative strategy is to replace X-rays with protons. However, this change is only an advantage if the proton machine employs a pencil scanning beam. Many proton facilities use passive modulation to produce a field of sufficient size, but the use of a scattering foil produces neutrons, which results in an effective dose to the patient higher than that characteristic of IMRT. The benefit of protons is only achieved if a scanning beam is used in which the doses are 10 times lower than with IMRT.

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          The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy.

          Out-of-field radiation doses to normal tissues may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Step-and-shoot intensity-modulated radiation therapy (IMRT), an increasingly popular treatment modality, yields higher out-of-field doses than do conventional treatments, because of an increase in required monitor units (beam-on time). We used published risk coefficients (NRCP Report 116) and out-of-field dose equivalents to multiple organ sites to estimate a conservative maximal risk of fatal secondary malignancy associated with 6 IMRT approaches and 1 conventional external-beam approach for prostate cancer. Depending on treatment energy, the IMRT treatments required 3.5-4.9 times as many monitor units to deliver as did the conventional treatment. The conservative maximum risk of fatal second malignancy was 1.7% for conventional radiation, 2.1% for IMRT using 10-MV X-rays, and 5.1% for IMRT using 18-MV X-rays. Intermediate risks were associated with IMRT using 6-MV X-rays: 2.9% for treatment with the Varian accelerator and 3.7% for treatment with the Siemens accelerator, as well as using 15-MV X-rays: 3.4% (Varian) and 4.0% (Siemens). The risk of fatal secondary malignancy differed substantially between IMRT and conventional radiation therapy for prostate cancer, as well as between different IMRT approaches. Perhaps this risk should be considered when choosing the optimal treatment technique and delivery system for patients who will undergo prostate radiation.
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            Radiation-induced second cancers: the impact of 3D-CRT and IMRT

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              Radiation dose and second cancer risk in patients treated for cancer of the cervix.

              The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.
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                Author and article information

                Journal
                International Journal of Radiation Oncology*Biology*Physics
                International Journal of Radiation Oncology*Biology*Physics
                Elsevier BV
                03603016
                May 2006
                May 2006
                : 65
                : 1
                : 1-7
                Article
                10.1016/j.ijrobp.2006.01.027
                16618572
                4d9e0968-65cf-4d76-bf73-b58f1e38b8ba
                © 2006

                https://www.elsevier.com/tdm/userlicense/1.0/

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