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.
Hall
Eric J
EJ
Center for Radiological Research, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ejh1@columbia.edu
Wuu
Cheng-Shie
CS
D000230:Adenocarcinoma / Q000532:radiotherapy; D000818:Animals; D002277:Carcinoma / Q000209:etiology / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D015994:Incidence; D007953:Leukemia, Radiation-Induced / Q000453:epidemiology / Q000209:etiology; D008297:Male; D009374:Neoplasms, Experimental / Q000209:etiology; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology*; D009689:Nuclear Warfare; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D011833:Radiation Injuries, Experimental / Q000209:etiology; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D011882:Radiotherapy, High-Energy / Q000009:adverse effects* / Q000295:instrumentation / Q000379:methods; D012306:Risk; D012509:Sarcoma / Q000209:etiology; D017741:Survivors; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy