## 3 Radiotherapy for Rectal Cancer
### Comparison of Radiotherapy Techniques  
Modern irradiation techniques, IMRT and volumetric modulated arc therapy (VMAT), may improve dose conformability while reducing the radiation exposure to organs at risk (OARs) compared to the traditional 3D-CRT technique. The above is illustrated in Figure 1. The VMAT and 3D-CRT plans for rectal carcinoma of this figure were created on an XCAT phantom simulating an average male adult patient. Six-MV photons were used for both treatment plans to deliver a target dose of 45 Gy. The 3D-CRT plan comprised four fields and the VMAT plan consisted of two full arcs of 360\({}^{\circ}\). The high-dose region in the VMAT plan better conforms to the shape of the target and gives more sparing of the radiosensitive urinary bladder and bowel than the 3D-CRT. [PERSON] et al. [41] have also demonstrated a significant reduction in the bowel volume receiving 45-50 Gy with IMRT, potentially lowering bowel toxicity. [PERSON] et al. [42] compared IMRT with 3D-CRT as neoadjuvant therapy with concurrent chemotherapy in 128 patients with locally advanced rectal cancer, finding that IMRT was associated with significantly less toxicity and improved partial responses. [PERSON] et al. [43] conducted a Phase 2 trial with 23 patients treated with concurrent capecitabine and dose-escalated IMRT (55 Gy in 25 fractions), reporting a 35% pathological complete response rate, 65% tumor downstaging, no local recurrences, and only one case (5%) of grade 3 radiation proctitis at a median follow-up of 38.2 months. The NationalComprehensive Cancer Network (NCCN) [3] recommends highly conformal techniques, with IMRT particularly preferred for reirradiation of recurrent patients. It may also be considered for patients with distal rectal or anal adenocarcinomas involving the inguinal lymph nodes, or for those who refuse or are not candidates for surgery. For the latter cohort, chemo-IMRT has been shown to be safe and is associated with high rates of complete responses [43]. Risk of Second Primary Cancers Following Radiotherapy for Rectal Carcinoma: A Review of Epidemiological Studies  
Several epidemiological studies have examined the risk of secondary cancer development following irradiation for various malignancies; however, few specifically focus on the effects of RT for rectal carcinomas. [PERSON] et al. [15] analyzed data from two Swedish randomized trials: the Uppsala Trial (preoperative RT vs. postoperative RT for stage II and III disease) and the Swedish Rectal Cancer Trial (preoperative RT vs. surgery alone), involving nearly 1600 patients. In this cohort, 122 new invasive cancers were diagnosed in 115 patients. These cancers  
Figure 1: Exemplary isodose distribution presented as a color-wash pattern for (**a**) 3D-CRT and (**b**) VMAT plans from 13.5 Gy (dark blue) to 42.75 Gy (orange). The target volume, right femoral head, left femoral head, bowel, and urinary bladder are shown in red, black, brown, green, and yellow colors on a pelvic CT scan. The plans were generated on a computerized XCAT phantom representing an average adult man. primarily affect the prostate, colon, and urinary bladder. The irradiated group showed a significantly increased risk of secondary cancers, with a relative risk (RR) of 1.85 compared to the non-irradiated group. Secondary cancers predominantly developed within or adjacent to the radiation fields (RR = 2.04), but not outside of them (RR = 1.78). The increased risk from RT was significant only for latency periods of 5 and 10 years, with a median latency time of 6.5 years. [PERSON] et al. [44] extended the analysis to include these two trials, as well as three additional Swedish randomized trials and data from the Swedish Colorectal Cancer Registry, encompassing a total of 13,457 patients. Of these, 7024 had received RT, and 6433 had undergone surgery only. Most patients received short-course RT (87.3%). The median follow-up was 5.9 years (range 0.5-29.6) for the RT + surgery group and 5.1 years (range 0.5-30.6) for the surgery-alone group.