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

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.

[1]  Louis K. Wagner,et al.  Limitation of Exposure to Ionizing Radiation , 1994 .

[2]  M. Mathieu,et al.  Malignant breast tumors after radiotherapy for a first cancer during childhood. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  E. Hall,et al.  Radiation-induced second cancers: the impact of 3D-CRT and IMRT. , 2003, International journal of radiation oncology, biology, physics.

[4]  D. Brenner,et al.  Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells. , 2001, Cancer research.

[5]  J. G. Hoffman Radiation Biology and Cancer , 1960 .

[6]  A. Koehler,et al.  Measurement of neutron dose equivalent to proton therapy patients outside of the proton radiation field , 2002 .

[7]  R. A. Baker,et al.  Combined haploinsufficiency for ATM and RAD9 as a factor in cell transformation, apoptosis, and DNA lesion repair dynamics. , 2005, Cancer research.

[8]  P Fraser,et al.  Radiation dose and second cancer risk in patients treated for cancer of the cervix. , 1988, Radiation research.

[9]  A. B. Brill,et al.  NCRP Report No. 116, Limitation of Exposure to Ionizing Radiation National Council on Radiation Protection, Bethesda, MD, 88 pages, $22.50 , 1994 .

[10]  D. Kuban,et al.  The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy. , 2005, International journal of radiation oncology, biology, physics.

[11]  A R Hounsell,et al.  X-ray leakage considerations for IMRT. , 2001, The British journal of radiology.

[12]  H. Joensuu,et al.  Second cancer among long-term survivors from Hodgkin's disease. , 1998, International journal of radiation oncology, biology, physics.

[13]  D A Pierce,et al.  Radiation-Related Cancer Risks at Low Doses among Atomic Bomb Survivors , 2000, Radiation research.

[14]  D Verellen,et al.  Risk assessment of radiation-induced malignancies based on whole-body equivalent dose estimates for IMRT treatment in the head and neck region. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  E. Pedroni,et al.  Secondary neutron dose during proton therapy using spot scanning. , 2002, International journal of radiation oncology, biology, physics.

[16]  K. Kase,et al.  Measurements of dose from secondary radiation outside a treatment field. , 1983, International journal of radiation oncology, biology, physics.

[17]  R. Mohan,et al.  A Monte Carlo study of radiation transport through multileaf collimators. , 2001, Medical physics.

[18]  D Followill,et al.  Estimates of whole-body dose equivalent produced by beam intensity modulated conformal therapy. , 1997, International journal of radiation oncology, biology, physics.

[19]  D. Brenner,et al.  Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery , 2000, Cancer.