Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Evaluation of small bowel motion and feasibility of using the peritoneal space to replace bowel loops for dose constraints during intensity-modulated radiotherapy for rectal cancer

Evaluation of small bowel motion and feasibility of using the peritoneal space to replace bowel... Background: The goal of this study was to assess small bowel motion and explore the feasibility of using peritoneal space (PS) to replace bowel loops (BL) via the dose constraint method to spare the small bowel during intensity-modulated radiotherapy (IMRT) for rectal cancer. Methods: A total of 24 patients with rectal cancer who underwent adjuvant or neoadjuvant radiotherapy were selected. Weekly repeat CT scans from pre-treatment to the fourth week of treatment were acquired and defined as Plan, 1 W, 2 W, 3 W, and 4 W. The 4 weekly CT scans were co-registered to the Plan CT, BL and PS contours were delineated in all of the scans, an IMRT plan was designed on Plan CT using PS constraint method, and then copied to the 4 weekly CT scans. The dose-volume, normal tissue complication probability (NTCP) of the small bowel and their variations during treatment were evaluated. Results: Overall, 109 sets of CT scans from 24 patients were acquired, and 109 plans were designed and copied. The BL and PS volumes were 250.3 cc and 1339.3 cc. The V of BL and PS based plan of pre-treatment were 182.6 cc and 919.0 cc, the shift% of them were 28.9 and 11.3% during treatment (p = 0.000), which was less in the prone position than in the supine position (25.2% vs 32.1%, p = 0.000; 9.9% vs 14.9%, p = 0.000). The NTCP and NTCP C A based plan of pre-treatment were 2.0 and 59.2%, the shift% during treatment were 46.1 and 14.0% respectively. Majority of BL’sD and V were meet the safety standard during treatment using PS dose limit method except 3 max 15 times (3/109) of V and 5 times of D (5/109). 15 max (Continued on next page) * Correspondence: qianjianjun0628@aliyun.com; dryetian@126.com Siyuan Li and Yanping Gong are contributed equally to this study. Department of Radiotherapy & Oncology, Second Affiliated Hospital of Soochow University, Institute of Radiotherapy and Oncology, Soochow University, Suzhou Key Laboratory for Radiation Oncology, Suzhou 215004, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. Radiation Oncology (2020) 15:211 Page 2 of 10 (Continued from previous page) Conclusions: This study indicated that small bowel motion may lead to uncertainties in its dose volume and NTCP evaluation during IMRT for rectal cancer. The BL movements were significantly greater than PS, and the prone position was significantly less than the supine position. It is feasibility of using PS to replace BL to spare the small bowel, V < 830 cc is the dose constraint standard. Keywords: Rectal cancer, Intensity modulated radiotherapy (IMRT), Small bowel, Bowel loops, Peritoneal space, Normal tissue complication probability (NTCP) Background for dose constraints to provide an optimised method of Radiochemotherapy is a widely accepted treatment mode sparing the small bowel during IMRT for rectal cancer. in patients with locally advanced rectal cancer. It can result in a significant reduction in the local recurrence Methods rate by up to 30% and improve the 5-year disease-free Patients survival rate [1–6]. The ethics board of the hospital approved the present Although radiochemotherapy can help cure many study, and all of the investigations were conducted in ac- rectal cancer survivors, acute and chronic intestinal side cordance with the relevant guidelines and regulations. effects (12–50%) such as diarrhoea, faecal incontinence, From March 2014 to March 2016, 24 patients with rectal and late small bowel obstructions have attracted increas- cancer who underwent adjuvant or neoadjuvant radio- ing attention because they may affect patients’ quality of therapy were selected. The patient characteristics are life and even interrupt treatment [7–10]. Studies have summarised in Table 1. shown that the irradiated small bowel volume is closely related to toxicity caused by radiotherapy, so reducing Table 1 Patient characteristics its irradiated volume is the key approach to effectively Variable n % prevent and reduce toxicity [11, 12]. Although intensity- Gender modulated radiation therapy (IMRT) reduces the risk of radiation-induced toxicity, toxicity remains a significant Male 15 62.5 concern. Female 9 37.5 In 2010, the Quantitative Analysis of Normal Tissue Age (y) Effects in the Clinic (QUANTEC) review provided the Range 39–77 / available dose volume data for small bowel toxicity. Median 58.5 / Acute small bowel injury has been described with a T stage threshold dose of grade 3 or greater toxicity when 120 cc volume of individually contoured bowel loops (BLs) T2 4 16.7 receive ≥15 Gy or when 195 cc of the contoured periton- T3 18 75.0 eal space (PS) receives ≥45 Gy [13, 14]. These are T4 2 8.3 commonly incorporated into radiotherapy protocols in N stage clinical practise. N0 8 33.3 Contouring the PS and BL are two primary ways to N1 13 54.2 evaluate the small bowel dose volume [15, 16]. However, the small bowel is always in motion and there may be N2 3 12.5 uncertainties in dose volume evaluations. The character- Clinical stage istics of narrow high dose distribution in IMRT technol- II 10 41.7 ogy will further increase this uncertainty. III 14 58.3 PS contouring has the advantages of accuracy, con- Treatment position venience, and repeatability compared with BL contour- Supine 12 50.0 ing. This volume can allow the small bowel to lie at any point during treatment and can mitigate the impact of Prone 12 50.0 small bowel movements. The scope of this study was to Radiotherapy quantify the impact of small bowel movements on the Adjuvant 16 66.7 dose volume and normal tissue complication probability Neoadjuvant 8 33.3 (NTCP) estimates and feasibility of using PS replace BL Li et al. Radiation Oncology (2020) 15:211 Page 3 of 10 Planning CT Target volume definition and treatment planning design CT scans (3 mm thick slices) of the patients’ whole The target volume was delineated per the RTOG and abdomen and pelvis were obtained with the treatment NCCN guidelines [18, 19]. The clinical target volume position on a Siemens Emotion-Duo CT simulator. (CTV) included the lymphatic drainage area of the Standard commercial immobilisation devices were perirectal lymph nodes, presacral lymph nodes, and applied. A carbon fibre frame and thermoplastic mask internal iliac lymph nodes, and some patients’ external fixation (Pelvicast system, Orfit, Wijnegem, Belgium) iliac lymph nodes were included. A margin of 1 cm in was used. The patients were in the supine position with the cranial-caudal direction and 0.5 cm in the anterior- a pillow under their heads. Their knees and ankles were posterior and lateral directions was given to the CTV to supported with vacuum cushions, and their arms resting form the PTV. The prescription was 50 Gy in 25 frac- on their chests. In the prone position, a belly board tions to the PTV. In the Pinnacle 9.0 treatment planning (Civco Medical Solutions, Coralville, IA, USA) was ap- system, 7 field IMRT plans used the PS (V < 830 cc) plied to allow the abdomen to extend into its aperture. dose constraints were designed [16]. The plans used a 6 The patients were instructed to empty the bladder an MV X-ray CC convolution algorithm and a 0.3 cm com- hour before CT simulation. Gastrografin solution (600 putational grid. An Elekta Synergy accelerator and 40 mL) was administered orally an hour before scanning to pairs of MLCs were selected. Dose constraints of V < better visualise the small bowel for delineation. CT scans 50% and V < 5% were used for the bladder and bilateral were subsequently imported into the treatment planning femoral head respectively. The target dose coverage re- system (Pinnacle 9.0, Philips Radiation Oncology, Fitch- quired more than 95% of the PTV covered by 100% of burg, MA. USA) for target delineation and treatment the prescription dose and a maximum dose (D )<54 max planning design. After the plan was confirmed, the pa- Gy inside and outside the PTV. Subsequently, the IMRT tients were treated at the Medical Synergy Accelerator plans from the Plan CT were copied to the 1-4 W CT (Elekta Synergy, Elekta Oncology Systems, Crawley, UK), images which had co-registered to the Plan CT. and when treatment they were required to keep their bladder moderately filled similar to simulation. CT im- Evaluation of small bowel dose volume ages were obtained and defined as 1 W, 2 W, 3 W, and 4 The absolute irradiated volume (cc) of the small bowel W, respectively, on the Friday of weeks 1–4 during treat- was described by its volume exposed to 5–50 Gy with 5 ment under the same scanning conditions. Subsequently, Gy intervals. Each patient’s small bowel volume (or irra- the 4 weekly CT scans were automatically co-registered diated volume) was expressed by the mean value over to the Plan CT respectively based on pelvic bone anat- their CT images. All of the patients’ small bowel omy, algorithm of Normalized Mutual Information in volumes (or irradiated volumes) during treatment were treatment planning system was used. expressed as their median volume values. Evaluation of small bowel motion Delineation of PS and BL The shift% was used to describe the small bowel move- Per the delineation methods of small bowel from RTOG ments, and shift% = SD/mean [20]. The SD and mean [17] and Robyn B [16], BL and PS were delineated for were the standard deviation and mean of the small each patient’s group of CT images. BL was delineated bowel volume (or irradiated volume) from all of the CT along the bowel loop’s outer surface based on the images. The variations among the patients were contrast effect of Gastrografin solution and excluding expressed by their median values. A larger shift% signi- the colon. The upper boundary was 1 cm above the fied greater motion of the small bowel during treatment. superior level of the planning target volume (PTV), and the lower boundary was delineation of the small bowel NTCP prediction of small bowels until it ended. For the PS, the anterior and bilateral The Lyman-Kutcher-Burman (LKB) calculation module boundaries were the inner surface of the abdominal in Pinnacle 9.0 was used to predict chronic complica- muscles, the posterior boundary was the vertebral body, tions of the small bowel (called NTCP )[21–23]. The n sacrum, or sigmoid colon. The upper boundary was 1 (volume factor), m (slope of dose response curve), and cm above the superior PTV level. The lower boundary TD (mean dose of 50% complication probability) pa- was parallel to the inferior sigmoid colon level. The PS rameters were set to 0.15, 0.16, and 55 Gy, respectively included the small bowel and colon, but did not include [24]. The complications were defined as small bowel ob- the bladder, ovary, and uterus. A window width of 600 structions, perforations, or fistulas. Logistic formula k − 1 and window level of 40 were selected for delineation of NTCP = (1 + (V /V) ) was used to calculate the acute the BL and PS and were completed by the same senior toxicity of the small bowel based on its V (called attending physician. NTCP ), where V and k were 130 cc and 1.1, A 50 Li et al. Radiation Oncology (2020) 15:211 Page 4 of 10 respectively [25]. Each patient’s NTCP was expressed by Statistical analysis the mean value over their all of the CT images. The SPSS 19.0 software was used for the data analysis. Sigma NTCP of all of the patients during treatment was Plot 10.0 and Microsoft Excel 2007 were used for figure expressed by their median values. The shift% here was plotting. A paired sample t-test was used to compare the used to describe the NTCP variations during treatment, differences between the two groups’ data, and their and shift% = SD/mean. correlation was analysed via Pearson’s correlation coeffi- cient. A two-tailed value of p < 0.05 was considered statistically significant. Safety assessment of small bowel during treatment V < 275 cc from Robyn B et al. [16] and D ≦54Gy Results 15 max were used as the criteria for safety evaluation of the PS and BL contours and treatment plans small bowel during treatment. The small bowel was at Figure 1 shows an example of a rectal cancer patient’s risk when the value exceeded these criteria. PS and BL contours and dose distribution based on Fig. 1 An example of a rectal cancer patient’s PS and BL contours and dose distribution based on different CT scans during treatment. The green, blue, and orange contours represent PTV, PS, and BL, respectively. The innermost and outermost dose lines are 50 Gy and 30 Gy, respectively. Picture Plan, 1 W, 2 W, 3 W, 4 W show the variations of PS and BL’s contours and dose distribution during treatment, picture Field show the radiotherapy field setup Li et al. Radiation Oncology (2020) 15:211 Page 5 of 10 different CT scans during treatment. A total of 109 sets Evaluation of small bowel motion of CT images were obtained for 24 patients, including The shift% of the BL and PS volumes was 28.5% (11.8– 24 sets of Plan, 2 W, and 3 W scans, 14 sets of 1 W 80.8%) and 9.8% (2.8–38.7%), respectively. The move- scans, and 23 sets of 4 W scans. Overall, 218 contours ment of BL was significantly larger than PS (p = 0.000). containing the PS and BL were delineated for each pa- As shown in Fig. 2 and Table 2 and 3, the shift% of tient. The median PS volume was 1339.3 cc (537.3– dose-volume (V ) from 28.9–55.0% in BL was signifi- 5–50 2121.7 cc) and the median BL volume was 250.3 cc cantly larger than the PS of 7.9–23.8% (top picture of (81.0–590.8 cc) in all of the patients. A total of 24 sets of Fig. 2). The shift% of the BL and PS’sV were 28.9% IMRT plans were designed based on Plan CT (109 sets (4.8–72.2%) and 11.3% (3.2–42.8%) (p = 0.000) respect- of plans obtained after the plans copied to 1-4 W CT ively, and the shift% of V were 35.8% (3.8–88.8%) and scans). In plan of pre-treatment, the median V of the 14.4% (4.2–47.3%) respectively (p = 0.000). The shift% of PS was 919.0 cc (493.4–1324.6 cc), and 13 sets (13/24) the BL and PS’sV in the prone position was lower were V > 830 cc, all of the other dose constraints were than in the supine position (25.2% vs 32.1%, p = 0.000; met (the V of BL was≦275.71 cc). 9.9% vs 14.9%, p = 0.000). As shown in Fig. 3, there was Fig. 2 The shift% of the BL and PS’ dose-volume during treatment. The top picture show the difference of shift% between the BL and PS, dark blue and purple lines represent BL and PS respectively. The bottom picture show the difference of shift% between the supine and prone position, the red and dark blue lines represent shift% of BL in supine and prone position respectively, the purple and green lines represent shift% of PS in supine and prone position respectively Li et al. Radiation Oncology (2020) 15:211 Page 6 of 10 Table 2 The dose-volume and NTCP of BL and their shift% during treatment Variable Plan 1 W P 2W P 3W P 4W P Mean SD shift% 1 2 3 4 V (cc) 288.9 356.3 0.897 210.0 0.009 263.8 0.169 224.0 0.007 248.7 75.5 30.4% V (cc) 244.0 270.2 0.902 187.4 0.012 223.8 0.441 197.1 0.015 223.4 65.8 29.4% V (cc) 182.6 219.0 0.731 144.6 0.042 181.5 0.887 167.3 0.023 170.1 49.1 28.9% V (cc) 152.8 173.5 0.985 120.4 0.058 166.0 0.639 125.3 0.036 139.2 45.3 32.6% V (cc) 125.7 139.7 0.858 91.1 0.126 148.3 0.924 105.2 0.084 112.2 36.5 32.6% V (cc) 99.9 116.1 0.611 73.1 0.277 111.1 0.641 81.0 0.171 82.3 29.5 35.8% V (cc) 79.2 98.9 0.439 55.5 0.45 85.4 0.405 60.8 0.185 63.9 25.1 39.3% V (cc) 61.1 72.0 0.339 42.3 0.795 65.3 0.199 48.9 0.260 50.5 21.1 41.8% V (cc) 42.3 47.3 0.215 32.3 0.743 48.3 0.152 34.1 0.368 37.2 18.4 49.4% V (cc) 17.8 23.2 0.088 19.2 0.131 22.1 0.028 18.5 0.539 21.6 11.9 55.0% NTCP (%) 59.2 63.9 0.958 52.9 0.046 59.1 0.891 56.9 0.017 56.5 7.9 14.0% NTCP (%) 2.0 2.0 0.110 3.0 0.034 4.0 0.007 3.0 0.323 2.8 1.3 46.1% The P ,P ,P , and P represent the comparison between the 1-4 W and Plan respectively 1 2 3 4 a significant correlation of V between the PS and BL Discussion during tratmnt, R = 0.455, p = 0.000. Because the small bowel is a radiosensitive organ, acute and chronic side effects may occur during rectal NTCP of small bowels cancer radiotherapy. The side effects can be reduced As shown in Table 2 (BL), the NTCP and NTCP by limiting the dose volume. However, evaluating the C A based plan of pre-treatment were 2.0 and 59.2%, the small bowel dose volume can be challenging. Charac- shift% during treatment were 46.1 and 14.0% respect- teristics of small bowel movement may weaken the ively. The difference of NTCP in 2 W and 4 W, and dose-limiting function. The small bowel loops do not difference of NTCP in 2–3 W were significant com- remain in the same positions at all times. They ex- pared with the plan pre-treatment (p < 0.05). As shown perience both oscillating displacements of the wall in Table 4, NTCP in supine patients were mildly larger due to peristalsis and large amplitude shifts due to than in prone patients, NTCP 4.9% vs 2.3% (p = 0.055) changes in content. The frequency of peristalsis can and NTCP 58.3% vs 55.7% (p = 0.109). reach 8–11 times per minute, and it can combine into complex forms of motion at different times and Safety assessment of small bowels during treatment spaces [26]. Small bowel movements have to be taken As shown in Fig. 4,V of the small bowel exceeded 275 into account when evaluating the dose volume by cc 3 times (3/109) during treatment, with a maximum of contouring the BL, while the peritoneal space can ac- 311.3 cc (over 13.18%). D of the small bowel > 54 Gy count for any potential region that may be occupied max 5 times, and the maximum value was 54.3 Gy. by the small bowel and covering its movements, so it Table 3 The dose-volume and its shift% of PS during treatment Variable plan 1 W P 2W P 3W P 4W P Mean SD shift% 1 2 3 4 V (cc) 1222.1 1444.7 0.147 1319.4 0.010 1359.5 0.083 1344.9 0.334 1328.6 105.1 7.9% V (cc) 1094.8 1319.9 0.054 1222.4 0.741 1104.6 0.921 1169.6 0.824 1217.8 101.9 8.4% V (cc) 919.0 1091.4 0.143 1098.1 0.015 1075.1 0.081 1082.1 0.351 1000.4 113.0 11.3% V (cc) 796.8 981.0 0.071 949.9 0.015 974.5 0.003 956.3 0.103 910.5 125.0 13.7% V (cc) 695.7 845.8 0.085 814.8 0.010 850.8 0.205 716.6 0.944 799.9 109.5 13.7% V (cc) 576.2 738.3 0.325 702.1 0.007 692.9 0.097 655.4 0.787 691.6 99.6 14.4% V (cc) 465.5 629.1 0.142 589.8 0.007 595.8 0.088 495.7 0.827 566.3 91.8 16.2% V (cc) 383.1 509.5 0.179 442.5 0.784 525.2 0.001 392.4 0.945 472.8 83.5 17.7% V (cc) 301.2 419.7 0.164 408.7 0.008 458.8 0.274 397.5 0.422 375.9 76.6 20.4% V (cc) 201.3 280.4 0.273 292.6 0.012 281.0 0.059 278.5 0.435 276.5 65.9 23.8% The P ,P ,P , and P represent the comparison between the 1-4 W and Plan respectively 1 2 3 4 Li et al. Radiation Oncology (2020) 15:211 Page 7 of 10 Fig. 3 Correlation of V between the PS and BL based on all of the CT scans replaces the BL for dose constraints with clinical bowel dose limitations should be carefully considered significance. when variations in the irradiation volume exceeded In this study, we first evaluated small bowel move- 20% [27]. Sanguineti et al. confirmed small bowel ment during treatment. Our results showed that vari- movement during prostate cancer radiotherapy by ations of all BL’s dose-volume were larger than 28%, continuous CT scanning. The results showed that while most of PS were below 20% (V ), and varia- 280 cc of the small bowel completely changed position 5–40 tions in prone position was significantly lower than in on planned CT, while only 20% remained in its the supine position (Fig. 2). Kvinnsland et al. studied original position [28]. the dose volume changes in the small bowel through The movement characteristics of the small bowel make 6 to 8 repeated CT scans in 10 patients with bladder it necessary to explore the reliability of the PS dose limit cancer. Their results showed that the relative standard method for small bowel sparing in IMRT. We used deviations of V ,V ,and V were 20, 24, and V < 275 cc and D ≦ 54Gy as the safety standard for 30.8 49.5 53.5 15 max 26% respectively. The authors believed that small small bowel during treatment, our results showed that majority of D and V were meet the safety standard, max 15 and indicating that the PS limit method was feasible for Table 4 Comparison of the small bowel dose-volume and small bowel sparing. NTCP between prone and supine patients Although the recommended dose constraint from Variable Supine position Prone position T p Robyn B was used in this study [16], there are slightly V (cc) 361.0 ± 113.2 208.0 ± 62.0 3.73 0.003 different research methods and irradiation techniques V (cc) 262.4 ± 78.5 191.4 ± 58.2 3.64 0.003 between the two. The PS dose and small bowel with V (cc) 176.6 ± 47.2 160.0 ± 51.1 1.84 0.092 15 PTV 45 Gy followed by tumour 5.4 Gy boost in the lit- erature may be lower than the present study (50 Gy PTV V (cc) 139.2 ± 44.7 134.7 ± 49.6 0.24 0.811 dose), while the four-field conformal technique may lead V (cc) 112.8 ± 41.9 110.3 ± 45.0 −0.28 0.777 to a higher dose than the IMRT technique used in this V (cc) 86.8 ± 38.6 76.6 ± 37.9 −0.28 0.779 study. V < 830 cc used as the dose constraint in this V (cc) 67.5 ± 34.1 60.3 ± 32.4 −0.02 0.980 study was relatively strict, approximately half of the V (cc) 52.4 ± 29.2 47.5 ± 28.9 0.06 0.953 plans (13/24) exceeded this standard, and the median V (cc) 38.8 ± 24.7 36.6 ± 24.4 0.18 0.856 45 value exceeded 10.71%. But even so, our results showed that the small bowel dose-volume could be further V (cc) 21.3 ± 20.4 23.0 ± 16.8 0.24 0.813 reduced by strictly limiting the PS dose, so it is appropri- D (cGy) 5341 ± 28 5341 ± 29 0.01 0.989 max ate to use V < 830 cc as the dose constraint. NTCP (%) 4.9 ± 2.9 2.3 ± 1.6 2.14 0.055 Patients with prior abdominal surgery are tend to NTCP (%) 58.3 ± 7.1 55.7 ± 9.8 1.74 0.109 experience greater rates of radiation-induced enteritis Li et al. Radiation Oncology (2020) 15:211 Page 8 of 10 Fig. 4 Safety assessment of the small bowel in 24 patients with rectal cancer during treatment. The top and bottom pictures are the D and max V estimation, respectively [29], it may also affect the movement of small bowel larger than 1 cm above the PTV should be adopted when during treatment. Because neoadjuvant treatment was using non-coplanar irradiation, while 2–5 cm should be not fully popularized in our hospital in 2014 and 2015, used for tomotherapy [17]. only 8 patients with neoadjuvant radiotherapy were The supine and prone position with a belly board involved in our study. Among the 8 patients, 3 were are common therapeutic positions in IMRT for rectal supine and 5 were prone position, the mixing of position cancer. Our results showed that dose-volume, NTCP effects make it difficult to compare the difference of and their variations of small bowel were less in prone small bowel movement between neoadjuvant and than supine position (Fig.2 and Table 4), consistent adjuvant radiotherapy patients. with previous studies [30–33]. Nevertheless, the Regarding the upper boundary of the PS and BL, design reproducibility and target dose coverage were Robyn B defined 1.5 cm above the PTV [16] while our significantly superior in the supine position. Some study used RTOG of 1.0 cm [17]. There was no substan- studies reported that patient positioning in RT for tial difference between 1.0 cm and 1.5 cm because rectal cancer patients may therefore be selected based coplanar IMRT technology and absolute volume (cc) on other factors such as the most comfortable evaluation were used in this study. An upper boundary position for the patients [33, 34]. Li et al. Radiation Oncology (2020) 15:211 Page 9 of 10 The PS defined in this study included the small bowel, Funding Jiangsu Provincial Medical Innovation Team (CXDT-37) and Jiangsu Provincial colon, and space between the intestines. The PS used Key Research and Development Programme (BE2018657). objectively in IMRT planning can reduce the overall PS dose volume, making it easier to reduce the small bowel Availability of data and materials The datasets used and analyzed during the current study are available from dose. It reduces high dose irradiation caused by small in- the corresponding author on reasonable request. testinal movement during treatment, so it has an advan- tage over the BL limit. Which uses only the small bowel Ethics approval and consent to participate The study was approved by the ethics committee of The Second Affiliated as the objective function. Further research showed that Hospital of Soochow University (2014047). there was a significant correlation of V between the PS and BL (Fig. 3, R = 0.455, p = 0.000), indicating that the Consent for publication PS can replace the BL as the objective function of the Not applicable. dose constraint in IMRT planning. However, when using Competing interests the PS limit, attention should be paid to the occurrence The authors declare that they have no competing interests. of PS dose hotspots in the absence of BL evaluation, es- Author details pecially when the dose limits are more stringent, and Department of Radiotherapy & Oncology, Second Affiliated Hospital of dose hotspots in PS must be evaluated and avoided to Soochow University, Institute of Radiotherapy and Oncology, Soochow prevent excessive small bowel irradiation. University, Suzhou Key Laboratory for Radiation Oncology, Suzhou 215004, China. Department of Oncology, Zhang Jia Gang First Hospital, Suzhou Our study may be too broad in showing the amplitude 215004, China. Department of Radiology, Second Affiliated Hospital of of small bowel movement, because involving neoadju- Soochow University, Suzhou 215004, China. vant and adjuvant therapy patients, which may be a limi- Received: 16 April 2020 Accepted: 20 August 2020 tation in our study. On the other hand, V as the primary dose-volume evaluation methods in this study was from conformal radiotherapy era, whether it is suit- References able for IMRT needs further clinical verification. Recent 1. Holyoake DLP, Partridge M, Hawkins MA, et al. Systematic review and meta- analysis of small bowel dose–volume and acute toxicity in conventionally- research shows that the moderate to high dose (V ) 20–40 fractionated rectal cancer radiotherapy. Radiother Oncol. 2019;138:38–44. trends toward being significantly associated with acute 2. Glimelius B, Tiret E, Cervantes A, Arnold D, ESMO Guidelines Working Group. toxity of small bowel in IMRT [35, 36]. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi81–8. 3. Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative Conclusions chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG Our findings demonstrated that small bowel motion C016): a multicentre, randomised trial. Lancet. 2009;373(9666):811–20. may lead to uncertainties in its dose volume and NTCP 4. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N assessment during IMRT for rectal cancer. The BL Engl J Med. 2004;351(17):1731–40. movements were significantly greater than the PS and 5. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. significantly less in the prone position than in the supine Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23. position. It is feasible to use the PS instead of the BL 6. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. limit to spare the small bowel. V < 830 cc can be used Preoperative versus postoperative chemoradiotherapy for locally advanced as the dose constraint standard. rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33. 7. Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman Abbreviations L, et al. Randomized phase III study comparing preoperative radiotherapy PS: Peritoneal space; BL: Bowel loops; IMRT: Intensity-modulated with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008; radiotherapy; NTCP: Normal tissue complication probability; 26(22):3687–94. QUANTEC: Quantitative Analysis of Normal Tissue Effects in the Clinic; 8. Bruheim K, Guren MG, Skovlund E, Hjermstad MJ, Dahl O, Frykholm G, et al. CT: Computed Tomography; RTOG: Radiation Therapy Oncology Group; Late side effects and quality of life after radiotherapy for rectal cancer. Int J PTV: Planning target volume; MLCs: Multi-leave collimators; NCCN: The Radiat Oncol Biol Phys. 2010;76(4):1005–11. National Comprehensive Cancer Network; CTV: Clinical target volume; 9. Jadon R, Higgins E, Hanna L, Evans M, Coles B, Staffurth J. A systematic D : Maximum dose; NTCP : Chronic complication probability of the small max C review of dose volume predictors and constraints for late bowel toxicity bowel; NTCP : Acute complication probability of the small bowel; V ,V , A 30.8 49.5 following pelvic radiotherapy. Radiat Oncol. 2019;14(1):57. V : Volume receiving at least 30.8Gy, 49.5Gy, 53.5Gy; V ,V ,V : Volume 53.5 10 15 30 10. Gandhi AK, Sharma DN, Rath GK, Julka PK, Subramani V, Sharma S, et al. receiving at least 10Gy, 15Gy, 30Gy Early clinical outcomes and toxicity of intensity modulated versus conventional pelvic radiation therapy for locally advanced cervix carcinoma: Acknowledgements a prospective randomized study. Int J Radiat Oncol Biol Phys. 2013;87(3): Not applicable. 542–8. 11. Robertson JM, Lockman D, Yan D, Wallace M. The dose volume relationship Authors’ contributions of small bowel irradiation and acute grade 3 diarrhea during SL, and YG: project conception and design, data collection, assembly, chemoradiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2008; analysis and interpretation, manuscript writing. YY, and QG: data collection 70(2):413–8. and assembly. JQ, and YT revised and approved the final manuscript. All 12. Reis T, Khazzaka E, Welzel G, Wenz F, Hofheinz RD, Mai S. Acute small-bowel authors read and approved the final manuscript. toxicity during neoadjuvant combined radiochemotherapy in locally Li et al. Radiation Oncology (2020) 15:211 Page 10 of 10 advanced rectal cancer: determination of optimal dose volume cut-off value 32. Sawayanagi S, Yamashita H, Ogita M, Kiritoshi T, Nakamoto T, Abe O, et al. predicting grade 2-3 diarrhoea. Radiat Oncol. 2015;10(1):30. Volumetric and dosimetric comparison of organs at risk between the prone 13. Kavanagh BD, Pan CC, Dawson LA, Das SK, Li XA, Haken RKT, et al. Radiation and supine positions in postoperative radiotherapy for prostate cancer. dose volume effects in the stomach and small bowel. Int J Radiat Oncol Radiat Oncol. 2018;13(1):70. Biol Phys. 2010;76(3 Suppl):S101–7. 33. Yang Y, Cai S, Zhao T, Peng Q, Qian J, Tian Y. Effect of prone and supine treatment positions for postoperative treatment of rectal cancer on target 14. Banerjee R, Chakraborty S, Nygren I, Sinha R. Small bowel dose parameters dose coverage and small bowel sparing using intensity-modulated radiation predicting grade ≥3 acute toxicity in rectal Cancer patients treated with therapy. Transl Cancer Res. 2019;9(2):491–9. neoadjuvant Chemoradiation: an independent validation study comparing 34. Frøseth TC, Strickert T, Solli KS, Salvesen O, Frykholm G, Reidunsdatter JR. A peritoneal cavity versus small bowel loop contouring techniques. Int J randomized study of the effect of patient positioning on setup Radiat Oncol Biol Phys. 2013;85(5):1225–31. reproducibility and dose distribution to organs at risk in radiotherapy of 15. Chi A, Nguyen NP, Xu J, Ji M, Tang J, Jin J, et al. Correlation of three rectal cancer patients. Radiat Oncol. 2015;10(1):217. different approaches of small bowel delineation and acute lower 35. Olsen J, Moughan J, Myerson R, Abitbol A, Doncals DE, Johnson D, et al. gastrointestinal toxicity in adjuvant pelvic intensity-modulated radiation Predictors of radiotherapy-related GI toxicity from anal Cancer DP-IMRT: therapy for endometrial cancer. Technol Cancer Res T. 2012;11(4):353–9. secondary analysis of NRG oncology RTOG 0529. Int J Radiat Oncol Biol 16. Robyn B, Santam C, Ian N, Richie S. Small bowel dose parameters predicting Phys. 2017;98(2):400–8. grade ≥3 acute toxicity in rectal Cancer patients treated with neoadjuvant 36. Sini C, Noris Chiorda B, Gabriele P, Sanguineti G, Morlino S, Badenchini F, Chemoradiation: an independent validation study comparing peritoneal et al. Patient-reported intestinal toxicity from whole pelvis intensity- cavity versus small bowel loop contouring techniques. Int J Radiat Oncol modulated radiotherapy: first quantification of bowel dose-volume effects. Biol Phys. 2012;85(5):1225–31. Radiother Oncol. 2017;124(2):269–301. 17. Gay HA, H Joseph B, Elizabeth O, Walter RB, Issam EN, Rawan A, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a radiation therapy oncology group consensus panel atlas. Int J Radiat Oncol Biol Phys. Publisher’sNote 2012;83(3):e353–62. Springer Nature remains neutral with regard to jurisdictional claims in 18. Myerson RJ, Garofalo MC, El Naqa I, Abrams RA, Apte A, Bosch WR, et al. published maps and institutional affiliations. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys. 2009;74(3):824–30. 19. Reyngold M, Niland J, Ter VA, Milne D, Milne BS, Cohen SJ, et al. Neoadjuvant radiotherapy use in locally advanced rectal cancer at NCCN member institutions. J Natl Compr Cancer Netw. 2014;12(2):235–43. 20. Nuyttens J, Robertson J, Yan D, Martinez A. The influence of small bowel motion on both a conventional three-field and intensity modulated radiation therapy (IMRT) for rectal cancer. Cancer Radiother. 2004;8(5):297–304. 21. Webb S, Nahum AE. A model for calculating tumor control probability in radiotherapy including the effects of inhomogeneous disributions of dose and clonogenic cell density. Phys Med Biol. 1993;38(6):653–66. 22. Burman C, Kutcher GJ, Emami B, Goitein M. Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys. 1991; 21(1):123–35. 23. Lyman JT, Wolbarst AB. Optimization of radiation therapy III: a method of assessing complication probabilities from dose volume histograms. Int J Radiat Oncol Biol Phys. 1987;13(1):103–9. 24. Cella L, Ciscognetti N, Martin G, Liuzzi R, Punzo G, Solla R, et al. Preoperative radiation treatment for rectal Cancer: comparison of target coverage and small bowel NTCP in conventional vs. 3D-conformal planning. Med Dosim. 2009;34(1):75–81. 25. Tho LM, Glegg M, Paterson J, Yap C, MacLeod A, McCabe M, et al. Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: investigating dose volume relationships and role for inverse planning. Int J Radiat Oncol Biol Phys. 2006;66(2):505–13. 26. Tai Y. Physiology (textbooks for colleges and universities in China, for clinical medicine of 8 years and 7 years). Beijing: People's HealthPublishing House; 2011. 27. Kvinnsland Y, Muren LP. The impact of organ motion on intestine doses and complication probabilities in radiotherapy of bladder cancer. Radiother Oncol. 2005;76(1):43–7. 28. Sanguineti G, Little M, Endres EJ, Sormani MP, Parker BC. Comparison of three strategies to delineate the bowel for whole pelvis IMRT of prostate cancer. Radiother Oncol. 2008;88(1):95–101. 29. Huang EY, Sung CC, Ko SF, Wang CJ, Yang KD. The different volume effects of small-bowel toxicity during pelvic irradiation between gynecologic patients with and without abdominal surgery: a prospective study with computed tomography-based dosimetry. Int J Radiat Oncol Biol Phys. 2007; 69(3):732–9. 30. Kószó R, Varga L, Fodor E, Kahán Z, Cserháti A, Hideghéty K, et al. Prone positioning on a belly board decreases rectal and bowel doses in pelvic intensity-modulated radiation therapy (IMRT) for prostate Cancer. Pathol Oncol Res. 2019;25(3):995–1002. 31. Koeck J, Kromer K, Lohr F, Baack T, Siebenlist K, Mai S, et al. Small bowel protection in IMRT for rectal cancer. Strahlenther Onkol. 2017;193(7):578–88. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

Evaluation of small bowel motion and feasibility of using the peritoneal space to replace bowel loops for dose constraints during intensity-modulated radiotherapy for rectal cancer

Download PDF
10 pages

Loading next page...
 
/lp/springer-journals/evaluation-of-small-bowel-motion-and-feasibility-of-using-the-FYWu3nm3DR

References (35)

Publisher
Springer Journals
Copyright
Copyright © The Author(s) 2020
eISSN
1748-717X
DOI
10.1186/s13014-020-01650-z
Publisher site
See Article on Publisher Site

Abstract

Background: The goal of this study was to assess small bowel motion and explore the feasibility of using peritoneal space (PS) to replace bowel loops (BL) via the dose constraint method to spare the small bowel during intensity-modulated radiotherapy (IMRT) for rectal cancer. Methods: A total of 24 patients with rectal cancer who underwent adjuvant or neoadjuvant radiotherapy were selected. Weekly repeat CT scans from pre-treatment to the fourth week of treatment were acquired and defined as Plan, 1 W, 2 W, 3 W, and 4 W. The 4 weekly CT scans were co-registered to the Plan CT, BL and PS contours were delineated in all of the scans, an IMRT plan was designed on Plan CT using PS constraint method, and then copied to the 4 weekly CT scans. The dose-volume, normal tissue complication probability (NTCP) of the small bowel and their variations during treatment were evaluated. Results: Overall, 109 sets of CT scans from 24 patients were acquired, and 109 plans were designed and copied. The BL and PS volumes were 250.3 cc and 1339.3 cc. The V of BL and PS based plan of pre-treatment were 182.6 cc and 919.0 cc, the shift% of them were 28.9 and 11.3% during treatment (p = 0.000), which was less in the prone position than in the supine position (25.2% vs 32.1%, p = 0.000; 9.9% vs 14.9%, p = 0.000). The NTCP and NTCP C A based plan of pre-treatment were 2.0 and 59.2%, the shift% during treatment were 46.1 and 14.0% respectively. Majority of BL’sD and V were meet the safety standard during treatment using PS dose limit method except 3 max 15 times (3/109) of V and 5 times of D (5/109). 15 max (Continued on next page) * Correspondence: qianjianjun0628@aliyun.com; dryetian@126.com Siyuan Li and Yanping Gong are contributed equally to this study. Department of Radiotherapy & Oncology, Second Affiliated Hospital of Soochow University, Institute of Radiotherapy and Oncology, Soochow University, Suzhou Key Laboratory for Radiation Oncology, Suzhou 215004, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. Radiation Oncology (2020) 15:211 Page 2 of 10 (Continued from previous page) Conclusions: This study indicated that small bowel motion may lead to uncertainties in its dose volume and NTCP evaluation during IMRT for rectal cancer. The BL movements were significantly greater than PS, and the prone position was significantly less than the supine position. It is feasibility of using PS to replace BL to spare the small bowel, V < 830 cc is the dose constraint standard. Keywords: Rectal cancer, Intensity modulated radiotherapy (IMRT), Small bowel, Bowel loops, Peritoneal space, Normal tissue complication probability (NTCP) Background for dose constraints to provide an optimised method of Radiochemotherapy is a widely accepted treatment mode sparing the small bowel during IMRT for rectal cancer. in patients with locally advanced rectal cancer. It can result in a significant reduction in the local recurrence Methods rate by up to 30% and improve the 5-year disease-free Patients survival rate [1–6]. The ethics board of the hospital approved the present Although radiochemotherapy can help cure many study, and all of the investigations were conducted in ac- rectal cancer survivors, acute and chronic intestinal side cordance with the relevant guidelines and regulations. effects (12–50%) such as diarrhoea, faecal incontinence, From March 2014 to March 2016, 24 patients with rectal and late small bowel obstructions have attracted increas- cancer who underwent adjuvant or neoadjuvant radio- ing attention because they may affect patients’ quality of therapy were selected. The patient characteristics are life and even interrupt treatment [7–10]. Studies have summarised in Table 1. shown that the irradiated small bowel volume is closely related to toxicity caused by radiotherapy, so reducing Table 1 Patient characteristics its irradiated volume is the key approach to effectively Variable n % prevent and reduce toxicity [11, 12]. Although intensity- Gender modulated radiation therapy (IMRT) reduces the risk of radiation-induced toxicity, toxicity remains a significant Male 15 62.5 concern. Female 9 37.5 In 2010, the Quantitative Analysis of Normal Tissue Age (y) Effects in the Clinic (QUANTEC) review provided the Range 39–77 / available dose volume data for small bowel toxicity. Median 58.5 / Acute small bowel injury has been described with a T stage threshold dose of grade 3 or greater toxicity when 120 cc volume of individually contoured bowel loops (BLs) T2 4 16.7 receive ≥15 Gy or when 195 cc of the contoured periton- T3 18 75.0 eal space (PS) receives ≥45 Gy [13, 14]. These are T4 2 8.3 commonly incorporated into radiotherapy protocols in N stage clinical practise. N0 8 33.3 Contouring the PS and BL are two primary ways to N1 13 54.2 evaluate the small bowel dose volume [15, 16]. However, the small bowel is always in motion and there may be N2 3 12.5 uncertainties in dose volume evaluations. The character- Clinical stage istics of narrow high dose distribution in IMRT technol- II 10 41.7 ogy will further increase this uncertainty. III 14 58.3 PS contouring has the advantages of accuracy, con- Treatment position venience, and repeatability compared with BL contour- Supine 12 50.0 ing. This volume can allow the small bowel to lie at any point during treatment and can mitigate the impact of Prone 12 50.0 small bowel movements. The scope of this study was to Radiotherapy quantify the impact of small bowel movements on the Adjuvant 16 66.7 dose volume and normal tissue complication probability Neoadjuvant 8 33.3 (NTCP) estimates and feasibility of using PS replace BL Li et al. Radiation Oncology (2020) 15:211 Page 3 of 10 Planning CT Target volume definition and treatment planning design CT scans (3 mm thick slices) of the patients’ whole The target volume was delineated per the RTOG and abdomen and pelvis were obtained with the treatment NCCN guidelines [18, 19]. The clinical target volume position on a Siemens Emotion-Duo CT simulator. (CTV) included the lymphatic drainage area of the Standard commercial immobilisation devices were perirectal lymph nodes, presacral lymph nodes, and applied. A carbon fibre frame and thermoplastic mask internal iliac lymph nodes, and some patients’ external fixation (Pelvicast system, Orfit, Wijnegem, Belgium) iliac lymph nodes were included. A margin of 1 cm in was used. The patients were in the supine position with the cranial-caudal direction and 0.5 cm in the anterior- a pillow under their heads. Their knees and ankles were posterior and lateral directions was given to the CTV to supported with vacuum cushions, and their arms resting form the PTV. The prescription was 50 Gy in 25 frac- on their chests. In the prone position, a belly board tions to the PTV. In the Pinnacle 9.0 treatment planning (Civco Medical Solutions, Coralville, IA, USA) was ap- system, 7 field IMRT plans used the PS (V < 830 cc) plied to allow the abdomen to extend into its aperture. dose constraints were designed [16]. The plans used a 6 The patients were instructed to empty the bladder an MV X-ray CC convolution algorithm and a 0.3 cm com- hour before CT simulation. Gastrografin solution (600 putational grid. An Elekta Synergy accelerator and 40 mL) was administered orally an hour before scanning to pairs of MLCs were selected. Dose constraints of V < better visualise the small bowel for delineation. CT scans 50% and V < 5% were used for the bladder and bilateral were subsequently imported into the treatment planning femoral head respectively. The target dose coverage re- system (Pinnacle 9.0, Philips Radiation Oncology, Fitch- quired more than 95% of the PTV covered by 100% of burg, MA. USA) for target delineation and treatment the prescription dose and a maximum dose (D )<54 max planning design. After the plan was confirmed, the pa- Gy inside and outside the PTV. Subsequently, the IMRT tients were treated at the Medical Synergy Accelerator plans from the Plan CT were copied to the 1-4 W CT (Elekta Synergy, Elekta Oncology Systems, Crawley, UK), images which had co-registered to the Plan CT. and when treatment they were required to keep their bladder moderately filled similar to simulation. CT im- Evaluation of small bowel dose volume ages were obtained and defined as 1 W, 2 W, 3 W, and 4 The absolute irradiated volume (cc) of the small bowel W, respectively, on the Friday of weeks 1–4 during treat- was described by its volume exposed to 5–50 Gy with 5 ment under the same scanning conditions. Subsequently, Gy intervals. Each patient’s small bowel volume (or irra- the 4 weekly CT scans were automatically co-registered diated volume) was expressed by the mean value over to the Plan CT respectively based on pelvic bone anat- their CT images. All of the patients’ small bowel omy, algorithm of Normalized Mutual Information in volumes (or irradiated volumes) during treatment were treatment planning system was used. expressed as their median volume values. Evaluation of small bowel motion Delineation of PS and BL The shift% was used to describe the small bowel move- Per the delineation methods of small bowel from RTOG ments, and shift% = SD/mean [20]. The SD and mean [17] and Robyn B [16], BL and PS were delineated for were the standard deviation and mean of the small each patient’s group of CT images. BL was delineated bowel volume (or irradiated volume) from all of the CT along the bowel loop’s outer surface based on the images. The variations among the patients were contrast effect of Gastrografin solution and excluding expressed by their median values. A larger shift% signi- the colon. The upper boundary was 1 cm above the fied greater motion of the small bowel during treatment. superior level of the planning target volume (PTV), and the lower boundary was delineation of the small bowel NTCP prediction of small bowels until it ended. For the PS, the anterior and bilateral The Lyman-Kutcher-Burman (LKB) calculation module boundaries were the inner surface of the abdominal in Pinnacle 9.0 was used to predict chronic complica- muscles, the posterior boundary was the vertebral body, tions of the small bowel (called NTCP )[21–23]. The n sacrum, or sigmoid colon. The upper boundary was 1 (volume factor), m (slope of dose response curve), and cm above the superior PTV level. The lower boundary TD (mean dose of 50% complication probability) pa- was parallel to the inferior sigmoid colon level. The PS rameters were set to 0.15, 0.16, and 55 Gy, respectively included the small bowel and colon, but did not include [24]. The complications were defined as small bowel ob- the bladder, ovary, and uterus. A window width of 600 structions, perforations, or fistulas. Logistic formula k − 1 and window level of 40 were selected for delineation of NTCP = (1 + (V /V) ) was used to calculate the acute the BL and PS and were completed by the same senior toxicity of the small bowel based on its V (called attending physician. NTCP ), where V and k were 130 cc and 1.1, A 50 Li et al. Radiation Oncology (2020) 15:211 Page 4 of 10 respectively [25]. Each patient’s NTCP was expressed by Statistical analysis the mean value over their all of the CT images. The SPSS 19.0 software was used for the data analysis. Sigma NTCP of all of the patients during treatment was Plot 10.0 and Microsoft Excel 2007 were used for figure expressed by their median values. The shift% here was plotting. A paired sample t-test was used to compare the used to describe the NTCP variations during treatment, differences between the two groups’ data, and their and shift% = SD/mean. correlation was analysed via Pearson’s correlation coeffi- cient. A two-tailed value of p < 0.05 was considered statistically significant. Safety assessment of small bowel during treatment V < 275 cc from Robyn B et al. [16] and D ≦54Gy Results 15 max were used as the criteria for safety evaluation of the PS and BL contours and treatment plans small bowel during treatment. The small bowel was at Figure 1 shows an example of a rectal cancer patient’s risk when the value exceeded these criteria. PS and BL contours and dose distribution based on Fig. 1 An example of a rectal cancer patient’s PS and BL contours and dose distribution based on different CT scans during treatment. The green, blue, and orange contours represent PTV, PS, and BL, respectively. The innermost and outermost dose lines are 50 Gy and 30 Gy, respectively. Picture Plan, 1 W, 2 W, 3 W, 4 W show the variations of PS and BL’s contours and dose distribution during treatment, picture Field show the radiotherapy field setup Li et al. Radiation Oncology (2020) 15:211 Page 5 of 10 different CT scans during treatment. A total of 109 sets Evaluation of small bowel motion of CT images were obtained for 24 patients, including The shift% of the BL and PS volumes was 28.5% (11.8– 24 sets of Plan, 2 W, and 3 W scans, 14 sets of 1 W 80.8%) and 9.8% (2.8–38.7%), respectively. The move- scans, and 23 sets of 4 W scans. Overall, 218 contours ment of BL was significantly larger than PS (p = 0.000). containing the PS and BL were delineated for each pa- As shown in Fig. 2 and Table 2 and 3, the shift% of tient. The median PS volume was 1339.3 cc (537.3– dose-volume (V ) from 28.9–55.0% in BL was signifi- 5–50 2121.7 cc) and the median BL volume was 250.3 cc cantly larger than the PS of 7.9–23.8% (top picture of (81.0–590.8 cc) in all of the patients. A total of 24 sets of Fig. 2). The shift% of the BL and PS’sV were 28.9% IMRT plans were designed based on Plan CT (109 sets (4.8–72.2%) and 11.3% (3.2–42.8%) (p = 0.000) respect- of plans obtained after the plans copied to 1-4 W CT ively, and the shift% of V were 35.8% (3.8–88.8%) and scans). In plan of pre-treatment, the median V of the 14.4% (4.2–47.3%) respectively (p = 0.000). The shift% of PS was 919.0 cc (493.4–1324.6 cc), and 13 sets (13/24) the BL and PS’sV in the prone position was lower were V > 830 cc, all of the other dose constraints were than in the supine position (25.2% vs 32.1%, p = 0.000; met (the V of BL was≦275.71 cc). 9.9% vs 14.9%, p = 0.000). As shown in Fig. 3, there was Fig. 2 The shift% of the BL and PS’ dose-volume during treatment. The top picture show the difference of shift% between the BL and PS, dark blue and purple lines represent BL and PS respectively. The bottom picture show the difference of shift% between the supine and prone position, the red and dark blue lines represent shift% of BL in supine and prone position respectively, the purple and green lines represent shift% of PS in supine and prone position respectively Li et al. Radiation Oncology (2020) 15:211 Page 6 of 10 Table 2 The dose-volume and NTCP of BL and their shift% during treatment Variable Plan 1 W P 2W P 3W P 4W P Mean SD shift% 1 2 3 4 V (cc) 288.9 356.3 0.897 210.0 0.009 263.8 0.169 224.0 0.007 248.7 75.5 30.4% V (cc) 244.0 270.2 0.902 187.4 0.012 223.8 0.441 197.1 0.015 223.4 65.8 29.4% V (cc) 182.6 219.0 0.731 144.6 0.042 181.5 0.887 167.3 0.023 170.1 49.1 28.9% V (cc) 152.8 173.5 0.985 120.4 0.058 166.0 0.639 125.3 0.036 139.2 45.3 32.6% V (cc) 125.7 139.7 0.858 91.1 0.126 148.3 0.924 105.2 0.084 112.2 36.5 32.6% V (cc) 99.9 116.1 0.611 73.1 0.277 111.1 0.641 81.0 0.171 82.3 29.5 35.8% V (cc) 79.2 98.9 0.439 55.5 0.45 85.4 0.405 60.8 0.185 63.9 25.1 39.3% V (cc) 61.1 72.0 0.339 42.3 0.795 65.3 0.199 48.9 0.260 50.5 21.1 41.8% V (cc) 42.3 47.3 0.215 32.3 0.743 48.3 0.152 34.1 0.368 37.2 18.4 49.4% V (cc) 17.8 23.2 0.088 19.2 0.131 22.1 0.028 18.5 0.539 21.6 11.9 55.0% NTCP (%) 59.2 63.9 0.958 52.9 0.046 59.1 0.891 56.9 0.017 56.5 7.9 14.0% NTCP (%) 2.0 2.0 0.110 3.0 0.034 4.0 0.007 3.0 0.323 2.8 1.3 46.1% The P ,P ,P , and P represent the comparison between the 1-4 W and Plan respectively 1 2 3 4 a significant correlation of V between the PS and BL Discussion during tratmnt, R = 0.455, p = 0.000. Because the small bowel is a radiosensitive organ, acute and chronic side effects may occur during rectal NTCP of small bowels cancer radiotherapy. The side effects can be reduced As shown in Table 2 (BL), the NTCP and NTCP by limiting the dose volume. However, evaluating the C A based plan of pre-treatment were 2.0 and 59.2%, the small bowel dose volume can be challenging. Charac- shift% during treatment were 46.1 and 14.0% respect- teristics of small bowel movement may weaken the ively. The difference of NTCP in 2 W and 4 W, and dose-limiting function. The small bowel loops do not difference of NTCP in 2–3 W were significant com- remain in the same positions at all times. They ex- pared with the plan pre-treatment (p < 0.05). As shown perience both oscillating displacements of the wall in Table 4, NTCP in supine patients were mildly larger due to peristalsis and large amplitude shifts due to than in prone patients, NTCP 4.9% vs 2.3% (p = 0.055) changes in content. The frequency of peristalsis can and NTCP 58.3% vs 55.7% (p = 0.109). reach 8–11 times per minute, and it can combine into complex forms of motion at different times and Safety assessment of small bowels during treatment spaces [26]. Small bowel movements have to be taken As shown in Fig. 4,V of the small bowel exceeded 275 into account when evaluating the dose volume by cc 3 times (3/109) during treatment, with a maximum of contouring the BL, while the peritoneal space can ac- 311.3 cc (over 13.18%). D of the small bowel > 54 Gy count for any potential region that may be occupied max 5 times, and the maximum value was 54.3 Gy. by the small bowel and covering its movements, so it Table 3 The dose-volume and its shift% of PS during treatment Variable plan 1 W P 2W P 3W P 4W P Mean SD shift% 1 2 3 4 V (cc) 1222.1 1444.7 0.147 1319.4 0.010 1359.5 0.083 1344.9 0.334 1328.6 105.1 7.9% V (cc) 1094.8 1319.9 0.054 1222.4 0.741 1104.6 0.921 1169.6 0.824 1217.8 101.9 8.4% V (cc) 919.0 1091.4 0.143 1098.1 0.015 1075.1 0.081 1082.1 0.351 1000.4 113.0 11.3% V (cc) 796.8 981.0 0.071 949.9 0.015 974.5 0.003 956.3 0.103 910.5 125.0 13.7% V (cc) 695.7 845.8 0.085 814.8 0.010 850.8 0.205 716.6 0.944 799.9 109.5 13.7% V (cc) 576.2 738.3 0.325 702.1 0.007 692.9 0.097 655.4 0.787 691.6 99.6 14.4% V (cc) 465.5 629.1 0.142 589.8 0.007 595.8 0.088 495.7 0.827 566.3 91.8 16.2% V (cc) 383.1 509.5 0.179 442.5 0.784 525.2 0.001 392.4 0.945 472.8 83.5 17.7% V (cc) 301.2 419.7 0.164 408.7 0.008 458.8 0.274 397.5 0.422 375.9 76.6 20.4% V (cc) 201.3 280.4 0.273 292.6 0.012 281.0 0.059 278.5 0.435 276.5 65.9 23.8% The P ,P ,P , and P represent the comparison between the 1-4 W and Plan respectively 1 2 3 4 Li et al. Radiation Oncology (2020) 15:211 Page 7 of 10 Fig. 3 Correlation of V between the PS and BL based on all of the CT scans replaces the BL for dose constraints with clinical bowel dose limitations should be carefully considered significance. when variations in the irradiation volume exceeded In this study, we first evaluated small bowel move- 20% [27]. Sanguineti et al. confirmed small bowel ment during treatment. Our results showed that vari- movement during prostate cancer radiotherapy by ations of all BL’s dose-volume were larger than 28%, continuous CT scanning. The results showed that while most of PS were below 20% (V ), and varia- 280 cc of the small bowel completely changed position 5–40 tions in prone position was significantly lower than in on planned CT, while only 20% remained in its the supine position (Fig. 2). Kvinnsland et al. studied original position [28]. the dose volume changes in the small bowel through The movement characteristics of the small bowel make 6 to 8 repeated CT scans in 10 patients with bladder it necessary to explore the reliability of the PS dose limit cancer. Their results showed that the relative standard method for small bowel sparing in IMRT. We used deviations of V ,V ,and V were 20, 24, and V < 275 cc and D ≦ 54Gy as the safety standard for 30.8 49.5 53.5 15 max 26% respectively. The authors believed that small small bowel during treatment, our results showed that majority of D and V were meet the safety standard, max 15 and indicating that the PS limit method was feasible for Table 4 Comparison of the small bowel dose-volume and small bowel sparing. NTCP between prone and supine patients Although the recommended dose constraint from Variable Supine position Prone position T p Robyn B was used in this study [16], there are slightly V (cc) 361.0 ± 113.2 208.0 ± 62.0 3.73 0.003 different research methods and irradiation techniques V (cc) 262.4 ± 78.5 191.4 ± 58.2 3.64 0.003 between the two. The PS dose and small bowel with V (cc) 176.6 ± 47.2 160.0 ± 51.1 1.84 0.092 15 PTV 45 Gy followed by tumour 5.4 Gy boost in the lit- erature may be lower than the present study (50 Gy PTV V (cc) 139.2 ± 44.7 134.7 ± 49.6 0.24 0.811 dose), while the four-field conformal technique may lead V (cc) 112.8 ± 41.9 110.3 ± 45.0 −0.28 0.777 to a higher dose than the IMRT technique used in this V (cc) 86.8 ± 38.6 76.6 ± 37.9 −0.28 0.779 study. V < 830 cc used as the dose constraint in this V (cc) 67.5 ± 34.1 60.3 ± 32.4 −0.02 0.980 study was relatively strict, approximately half of the V (cc) 52.4 ± 29.2 47.5 ± 28.9 0.06 0.953 plans (13/24) exceeded this standard, and the median V (cc) 38.8 ± 24.7 36.6 ± 24.4 0.18 0.856 45 value exceeded 10.71%. But even so, our results showed that the small bowel dose-volume could be further V (cc) 21.3 ± 20.4 23.0 ± 16.8 0.24 0.813 reduced by strictly limiting the PS dose, so it is appropri- D (cGy) 5341 ± 28 5341 ± 29 0.01 0.989 max ate to use V < 830 cc as the dose constraint. NTCP (%) 4.9 ± 2.9 2.3 ± 1.6 2.14 0.055 Patients with prior abdominal surgery are tend to NTCP (%) 58.3 ± 7.1 55.7 ± 9.8 1.74 0.109 experience greater rates of radiation-induced enteritis Li et al. Radiation Oncology (2020) 15:211 Page 8 of 10 Fig. 4 Safety assessment of the small bowel in 24 patients with rectal cancer during treatment. The top and bottom pictures are the D and max V estimation, respectively [29], it may also affect the movement of small bowel larger than 1 cm above the PTV should be adopted when during treatment. Because neoadjuvant treatment was using non-coplanar irradiation, while 2–5 cm should be not fully popularized in our hospital in 2014 and 2015, used for tomotherapy [17]. only 8 patients with neoadjuvant radiotherapy were The supine and prone position with a belly board involved in our study. Among the 8 patients, 3 were are common therapeutic positions in IMRT for rectal supine and 5 were prone position, the mixing of position cancer. Our results showed that dose-volume, NTCP effects make it difficult to compare the difference of and their variations of small bowel were less in prone small bowel movement between neoadjuvant and than supine position (Fig.2 and Table 4), consistent adjuvant radiotherapy patients. with previous studies [30–33]. Nevertheless, the Regarding the upper boundary of the PS and BL, design reproducibility and target dose coverage were Robyn B defined 1.5 cm above the PTV [16] while our significantly superior in the supine position. Some study used RTOG of 1.0 cm [17]. There was no substan- studies reported that patient positioning in RT for tial difference between 1.0 cm and 1.5 cm because rectal cancer patients may therefore be selected based coplanar IMRT technology and absolute volume (cc) on other factors such as the most comfortable evaluation were used in this study. An upper boundary position for the patients [33, 34]. Li et al. Radiation Oncology (2020) 15:211 Page 9 of 10 The PS defined in this study included the small bowel, Funding Jiangsu Provincial Medical Innovation Team (CXDT-37) and Jiangsu Provincial colon, and space between the intestines. The PS used Key Research and Development Programme (BE2018657). objectively in IMRT planning can reduce the overall PS dose volume, making it easier to reduce the small bowel Availability of data and materials The datasets used and analyzed during the current study are available from dose. It reduces high dose irradiation caused by small in- the corresponding author on reasonable request. testinal movement during treatment, so it has an advan- tage over the BL limit. Which uses only the small bowel Ethics approval and consent to participate The study was approved by the ethics committee of The Second Affiliated as the objective function. Further research showed that Hospital of Soochow University (2014047). there was a significant correlation of V between the PS and BL (Fig. 3, R = 0.455, p = 0.000), indicating that the Consent for publication PS can replace the BL as the objective function of the Not applicable. dose constraint in IMRT planning. However, when using Competing interests the PS limit, attention should be paid to the occurrence The authors declare that they have no competing interests. of PS dose hotspots in the absence of BL evaluation, es- Author details pecially when the dose limits are more stringent, and Department of Radiotherapy & Oncology, Second Affiliated Hospital of dose hotspots in PS must be evaluated and avoided to Soochow University, Institute of Radiotherapy and Oncology, Soochow prevent excessive small bowel irradiation. University, Suzhou Key Laboratory for Radiation Oncology, Suzhou 215004, China. Department of Oncology, Zhang Jia Gang First Hospital, Suzhou Our study may be too broad in showing the amplitude 215004, China. Department of Radiology, Second Affiliated Hospital of of small bowel movement, because involving neoadju- Soochow University, Suzhou 215004, China. vant and adjuvant therapy patients, which may be a limi- Received: 16 April 2020 Accepted: 20 August 2020 tation in our study. On the other hand, V as the primary dose-volume evaluation methods in this study was from conformal radiotherapy era, whether it is suit- References able for IMRT needs further clinical verification. Recent 1. Holyoake DLP, Partridge M, Hawkins MA, et al. Systematic review and meta- analysis of small bowel dose–volume and acute toxicity in conventionally- research shows that the moderate to high dose (V ) 20–40 fractionated rectal cancer radiotherapy. Radiother Oncol. 2019;138:38–44. trends toward being significantly associated with acute 2. Glimelius B, Tiret E, Cervantes A, Arnold D, ESMO Guidelines Working Group. toxity of small bowel in IMRT [35, 36]. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi81–8. 3. Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative Conclusions chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG Our findings demonstrated that small bowel motion C016): a multicentre, randomised trial. Lancet. 2009;373(9666):811–20. may lead to uncertainties in its dose volume and NTCP 4. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N assessment during IMRT for rectal cancer. The BL Engl J Med. 2004;351(17):1731–40. movements were significantly greater than the PS and 5. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. significantly less in the prone position than in the supine Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23. position. It is feasible to use the PS instead of the BL 6. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. limit to spare the small bowel. V < 830 cc can be used Preoperative versus postoperative chemoradiotherapy for locally advanced as the dose constraint standard. rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33. 7. Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman Abbreviations L, et al. Randomized phase III study comparing preoperative radiotherapy PS: Peritoneal space; BL: Bowel loops; IMRT: Intensity-modulated with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008; radiotherapy; NTCP: Normal tissue complication probability; 26(22):3687–94. QUANTEC: Quantitative Analysis of Normal Tissue Effects in the Clinic; 8. Bruheim K, Guren MG, Skovlund E, Hjermstad MJ, Dahl O, Frykholm G, et al. CT: Computed Tomography; RTOG: Radiation Therapy Oncology Group; Late side effects and quality of life after radiotherapy for rectal cancer. Int J PTV: Planning target volume; MLCs: Multi-leave collimators; NCCN: The Radiat Oncol Biol Phys. 2010;76(4):1005–11. National Comprehensive Cancer Network; CTV: Clinical target volume; 9. Jadon R, Higgins E, Hanna L, Evans M, Coles B, Staffurth J. A systematic D : Maximum dose; NTCP : Chronic complication probability of the small max C review of dose volume predictors and constraints for late bowel toxicity bowel; NTCP : Acute complication probability of the small bowel; V ,V , A 30.8 49.5 following pelvic radiotherapy. Radiat Oncol. 2019;14(1):57. V : Volume receiving at least 30.8Gy, 49.5Gy, 53.5Gy; V ,V ,V : Volume 53.5 10 15 30 10. Gandhi AK, Sharma DN, Rath GK, Julka PK, Subramani V, Sharma S, et al. receiving at least 10Gy, 15Gy, 30Gy Early clinical outcomes and toxicity of intensity modulated versus conventional pelvic radiation therapy for locally advanced cervix carcinoma: Acknowledgements a prospective randomized study. Int J Radiat Oncol Biol Phys. 2013;87(3): Not applicable. 542–8. 11. Robertson JM, Lockman D, Yan D, Wallace M. The dose volume relationship Authors’ contributions of small bowel irradiation and acute grade 3 diarrhea during SL, and YG: project conception and design, data collection, assembly, chemoradiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2008; analysis and interpretation, manuscript writing. YY, and QG: data collection 70(2):413–8. and assembly. JQ, and YT revised and approved the final manuscript. All 12. Reis T, Khazzaka E, Welzel G, Wenz F, Hofheinz RD, Mai S. Acute small-bowel authors read and approved the final manuscript. toxicity during neoadjuvant combined radiochemotherapy in locally Li et al. Radiation Oncology (2020) 15:211 Page 10 of 10 advanced rectal cancer: determination of optimal dose volume cut-off value 32. Sawayanagi S, Yamashita H, Ogita M, Kiritoshi T, Nakamoto T, Abe O, et al. predicting grade 2-3 diarrhoea. Radiat Oncol. 2015;10(1):30. Volumetric and dosimetric comparison of organs at risk between the prone 13. Kavanagh BD, Pan CC, Dawson LA, Das SK, Li XA, Haken RKT, et al. Radiation and supine positions in postoperative radiotherapy for prostate cancer. dose volume effects in the stomach and small bowel. Int J Radiat Oncol Radiat Oncol. 2018;13(1):70. Biol Phys. 2010;76(3 Suppl):S101–7. 33. Yang Y, Cai S, Zhao T, Peng Q, Qian J, Tian Y. Effect of prone and supine treatment positions for postoperative treatment of rectal cancer on target 14. Banerjee R, Chakraborty S, Nygren I, Sinha R. Small bowel dose parameters dose coverage and small bowel sparing using intensity-modulated radiation predicting grade ≥3 acute toxicity in rectal Cancer patients treated with therapy. Transl Cancer Res. 2019;9(2):491–9. neoadjuvant Chemoradiation: an independent validation study comparing 34. Frøseth TC, Strickert T, Solli KS, Salvesen O, Frykholm G, Reidunsdatter JR. A peritoneal cavity versus small bowel loop contouring techniques. Int J randomized study of the effect of patient positioning on setup Radiat Oncol Biol Phys. 2013;85(5):1225–31. reproducibility and dose distribution to organs at risk in radiotherapy of 15. Chi A, Nguyen NP, Xu J, Ji M, Tang J, Jin J, et al. Correlation of three rectal cancer patients. Radiat Oncol. 2015;10(1):217. different approaches of small bowel delineation and acute lower 35. Olsen J, Moughan J, Myerson R, Abitbol A, Doncals DE, Johnson D, et al. gastrointestinal toxicity in adjuvant pelvic intensity-modulated radiation Predictors of radiotherapy-related GI toxicity from anal Cancer DP-IMRT: therapy for endometrial cancer. Technol Cancer Res T. 2012;11(4):353–9. secondary analysis of NRG oncology RTOG 0529. Int J Radiat Oncol Biol 16. Robyn B, Santam C, Ian N, Richie S. Small bowel dose parameters predicting Phys. 2017;98(2):400–8. grade ≥3 acute toxicity in rectal Cancer patients treated with neoadjuvant 36. Sini C, Noris Chiorda B, Gabriele P, Sanguineti G, Morlino S, Badenchini F, Chemoradiation: an independent validation study comparing peritoneal et al. Patient-reported intestinal toxicity from whole pelvis intensity- cavity versus small bowel loop contouring techniques. Int J Radiat Oncol modulated radiotherapy: first quantification of bowel dose-volume effects. Biol Phys. 2012;85(5):1225–31. Radiother Oncol. 2017;124(2):269–301. 17. Gay HA, H Joseph B, Elizabeth O, Walter RB, Issam EN, Rawan A, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a radiation therapy oncology group consensus panel atlas. Int J Radiat Oncol Biol Phys. Publisher’sNote 2012;83(3):e353–62. Springer Nature remains neutral with regard to jurisdictional claims in 18. Myerson RJ, Garofalo MC, El Naqa I, Abrams RA, Apte A, Bosch WR, et al. published maps and institutional affiliations. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys. 2009;74(3):824–30. 19. Reyngold M, Niland J, Ter VA, Milne D, Milne BS, Cohen SJ, et al. Neoadjuvant radiotherapy use in locally advanced rectal cancer at NCCN member institutions. J Natl Compr Cancer Netw. 2014;12(2):235–43. 20. Nuyttens J, Robertson J, Yan D, Martinez A. The influence of small bowel motion on both a conventional three-field and intensity modulated radiation therapy (IMRT) for rectal cancer. Cancer Radiother. 2004;8(5):297–304. 21. Webb S, Nahum AE. A model for calculating tumor control probability in radiotherapy including the effects of inhomogeneous disributions of dose and clonogenic cell density. Phys Med Biol. 1993;38(6):653–66. 22. Burman C, Kutcher GJ, Emami B, Goitein M. Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys. 1991; 21(1):123–35. 23. Lyman JT, Wolbarst AB. Optimization of radiation therapy III: a method of assessing complication probabilities from dose volume histograms. Int J Radiat Oncol Biol Phys. 1987;13(1):103–9. 24. Cella L, Ciscognetti N, Martin G, Liuzzi R, Punzo G, Solla R, et al. Preoperative radiation treatment for rectal Cancer: comparison of target coverage and small bowel NTCP in conventional vs. 3D-conformal planning. Med Dosim. 2009;34(1):75–81. 25. Tho LM, Glegg M, Paterson J, Yap C, MacLeod A, McCabe M, et al. Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: investigating dose volume relationships and role for inverse planning. Int J Radiat Oncol Biol Phys. 2006;66(2):505–13. 26. Tai Y. Physiology (textbooks for colleges and universities in China, for clinical medicine of 8 years and 7 years). Beijing: People's HealthPublishing House; 2011. 27. Kvinnsland Y, Muren LP. The impact of organ motion on intestine doses and complication probabilities in radiotherapy of bladder cancer. Radiother Oncol. 2005;76(1):43–7. 28. Sanguineti G, Little M, Endres EJ, Sormani MP, Parker BC. Comparison of three strategies to delineate the bowel for whole pelvis IMRT of prostate cancer. Radiother Oncol. 2008;88(1):95–101. 29. Huang EY, Sung CC, Ko SF, Wang CJ, Yang KD. The different volume effects of small-bowel toxicity during pelvic irradiation between gynecologic patients with and without abdominal surgery: a prospective study with computed tomography-based dosimetry. Int J Radiat Oncol Biol Phys. 2007; 69(3):732–9. 30. Kószó R, Varga L, Fodor E, Kahán Z, Cserháti A, Hideghéty K, et al. Prone positioning on a belly board decreases rectal and bowel doses in pelvic intensity-modulated radiation therapy (IMRT) for prostate Cancer. Pathol Oncol Res. 2019;25(3):995–1002. 31. Koeck J, Kromer K, Lohr F, Baack T, Siebenlist K, Mai S, et al. Small bowel protection in IMRT for rectal cancer. Strahlenther Onkol. 2017;193(7):578–88.

Journal

Radiation Oncology – Springer Journals

Published: Sep 1, 2020

There are no references for this article.