## 3 Radiotherapy for Rectal Cancer
### Dosimetric Studies  
The first theoretical cancer risk assessments associated with RT for carcinoma were made by [PERSON] et al. [17]. They used a non-linear model accounting for cell sterilization [67] and dose-volume histogram data from 3D-CRT and VMAT plans of 25 patients for estimating the risk for developing bone and soft tissue sarcomas and solid tumors in the bladder, colon, skin, small bowel, prostate, ovaries, and uterus. The highest excess risk was found for the bladder and colon. For VMAT delivered in 25 fractions of 1.8 Gy per fraction, the total lifetime risk for the development of secondary malignancies, as derived from the sum of the specific risks to the examined organs and tissues, was 2.3-3.0% depending upon the model parameters applied. The corresponding total risk from 3D-CRT was 2.0-2.7%. The use of a short RT course giving 25 Gy to the tumor in five fractions led to total risks up to 1.9% and 1.7% from pelvic VMAT and 3D-CRT, respectively. No statistically significant risk difference was found between the two treatment techniques.  
[PERSON] et al. [68] estimated the cancer risk to thirteen organs excluded from the treatment fields from 3D-CRT delivered with 15 or 18 MV photons, from 15 MV-VMAT and 18 MV-IMRT. Two linear models [57; 58] were employed for assessing the probability of carcinogenesis to out-of-field organs located in the pelvis, abdomen, thorax, and neck. The organ doses from neutrons were measured on a humanoid adult phantom and the photon doses were computed with the aid of an analytical model. For a 45 Gy tumor dose, the whole-body cancer risk from 3D-CRT varied from 0.3% to 2.3% depending on the photon energy used, the patient's gender, and the model used. Increased total risks of 0.9-4.2% and 1.1-4.4% were estimated for IMRT and VMAT, respectively.  
[PERSON] et al. [18] focused on the second-cancer risk to heavily irradiated organs such as the urinary bladder and bowel. IMRT and VMAT with 6 and 10 MV photons were generated for sixteen rectal patients needing preoperative RT for rectal cancer. A mechanistic model introduced by [PERSON] et al. [69] was used in this study. The effects of tumor dose fractionation and cell proliferation were taken into account by the cancer risk assessment. Conventionally fractionated treatment giving 50 Gy in 25 fractions and hypofractionated irradiation consisting of 5 fractions delivering a total target dose of 25 Gy were considered. The average lifetime cancer risk was assessed for four different patient ages from 45 to 60 years. The bladder cancer risk due to IMRT varied from 0.08% to 0.19% by the energy of the photon beams, the applied fractionated schedule, and the age of the patient at the time of treatment. The probability of bowel cancer induction was 0.05-0.14%. VMAT resulted in bladder and bowel cancer risks of 0.06-0.23% and 0.05-0.14%, respectively. Hypoffractionated IMRT and VMAT systematically elevated the bladder cancer risk compared to treatment delivered with the standard fractionation scheme. Similar bowel cancer risks were assessed for both fractionation schedules examined in this work.  
[PERSON] et al. [70] used different models to estimate the probability of carcinogenesis to organs adjacent to the treatment volume such as the bladder, small bowel, ovaries, uterus, skin, and kidneys for thirty women subjected to 3D-CRT for rectal carcinoma. Parts of these organs receive high radiation doses leading to mean organ doses up to 45.37 Gy. However, the models used in this work were designed for cancer risk assessments in the low-dose region. In accordance with [PERSON] et al. [71], we consider that a different approach should be used by the authors for assessing the probability of carcinogenesis in organs exposed to high therapeutic dose levels.