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      Second primary cancers after radiation for prostate cancer: A systematic review of the clinical data and impact of treatment technique

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          Abstract

          The development of a radiation induced second primary cancer (SPC) is one the most serious long term consequences of successful cancer treatment. This review aims to evaluate SPC in prostate cancer (PCa) patients treated with radiotherapy, and assess whether radiation technique influences SPC. A systematic review of the literature was performed to identify studies examining SPC in irradiated PCa patients. This identified 19 registry publications, 21 institutional series and 7 other studies. There is marked heterogeneity in published studies. An increased risk of radiation-induced SPC has been identified in several studies, particularly those with longer durations of follow-up. The risk of radiation-induced SPC appears small, in the range of 1 in 220 to 1 in 290 over all durations of follow-up, and may increase to 1 in 70 for patients followed up for more than 10 years, based on studies which include patients treated with older radiation techniques (i.e. non-conformal, large field). To date there are insufficient clinical data to draw firm conclusions about the impact of more modern techniques such as IMRT and brachytherapy on SPC risk, although limited evidence is encouraging. In conclusion, despite heterogeneity between studies, an increased risk of SPC following radiation for PCa has been identified in several studies, and this risk appears to increase over time. This must be borne in mind when considering which patients to irradiate and which techniques to employ.

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          Most cited references52

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          Radiation-induced second cancers: the impact of 3D-CRT and IMRT.

          Information concerning radiation-induced malignancies comes from the A-bomb survivors and from medically exposed individuals, including second cancers in radiation therapy patients. The A-bomb survivors show an excess incidence of carcinomas in tissues such as the gastrointestinal tract, breast, thyroid, and bladder, which is linear with dose up to about 2.5 Sv. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at higher doses. Some animal and human data suggest a decrease at higher doses, usually attributed to cell killing; other data suggest a plateau in dose. Radiotherapy patients also show an excess incidence of carcinomas, often in sites remote from the treatment fields; in addition there is an excess incidence of sarcomas in the heavily irradiated in-field tissues. The transition from conventional radiotherapy to three-dimensional conformal radiation therapy (3D-CRT) involves a reduction in the volume of normal tissues receiving a high dose, with an increase in dose to the target volume that includes the tumor and a limited amount of normal tissue. One might expect a decrease in the number of sarcomas induced and also (less certain) a small decrease in the number of carcinomas. All around, a good thing. By contrast, the move from 3D-CRT to intensity-modulated radiation therapy (IMRT) involves more fields, and the dose-volume histograms show that, as a consequence, a larger volume of normal tissue is exposed to lower doses. In addition, the number of monitor units is increased by a factor of 2 to 3, increasing the total body exposure, due to leakage radiation. Both factors will tend to increase the risk of second cancers. Altogether, IMRT is likely to almost double the incidence of second malignancies compared with conventional radiotherapy from about 1% to 1.75% for patients surviving 10 years. The numbers may be larger for longer survival (or for younger patients), but the ratio should remain the same.
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            Sarcoma arising in irradiated bone; report of 11 cases.

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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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                Author and article information

                Contributors
                Journal
                Radiother Oncol
                Radiother Oncol
                Radiotherapy and Oncology
                Elsevier Scientific Publishers
                0167-8140
                1879-0887
                1 February 2014
                February 2014
                : 110
                : 2
                : 213-228
                Affiliations
                [a ]St. James’s Institute of Oncology, Leeds, UK
                [b ]Mount Vernon Cancer Centre, Northwood, UK
                [c ]Klinik fur Strahlentherapie, Kiel, Germany
                [d ]Institute Verbeeten, Tilburg, Netherlands
                Author notes
                [* ]Corresponding author. Address: St. James’s Institute of Oncology, Beckett St, Leeds LS9 7TF, UK. Ann.Henry@ 123456leedsth.nhs.uk
                Article
                S0167-8140(13)00657-9
                10.1016/j.radonc.2013.12.012
                3988985
                24485765
                a090a77a-91f0-4ba2-b3d5-ec802a2ef99b
                © 2014 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 1 February 2013
                : 18 December 2013
                : 25 December 2013
                Categories
                Systematic Review

                Oncology & Radiotherapy
                prostate cancer,second primary cancer,systematic review
                Oncology & Radiotherapy
                prostate cancer, second primary cancer, systematic review

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