Radiation Dose–Volume Effects in Radiation-Induced Rectal Injury

Abstract

The available dose/volume/outcome data for rectal injury were reviewed. The volume of rectum receiving ≥60Gy is consistently associated with the risk of Grade ≥2 rectal toxicity or rectal bleeding. Parameters for the Lyman-Kutcher-Burman normal tissue complication probability model from four clinical series are remarkably consistent, suggesting that high doses are predominant in determining the risk of toxicity. The best overall estimates (95% confidence interval) of the Lyman-Kutcher-Burman model parameters are n = 0.09 (0.04-0.14); m = 0.13 (0.10-0.17); and TD 50 = 76.9 (73.7-80.1) Gy. Most of the models of late radiation toxicity come from three-dimensional conformal radiotherapy dose-escalation studies of early-stage prostate cancer. It is possible that intensity-modulated radiotherapy or proton beam dose distributions require modification of these models because of the inherent differences in low and intermediate dose distributions. KeywordsRectum; Radiation injury; NTCP CLINICAL SIGNIFICANCEApproximately 300,000 patients undergo pelvic radiotherapy (RT) worldwide annually (1). Depending on the techniques and doses used, patients may experience a permanent change in their bowel habits. ENDPOINTSAcute rectal effects occur during or soon after RT and typically include softer or diarrhealike stools, pain, a sense of rectal distention with cramping, and frequency. Occasionally, superficial ulceration causes bleeding that may require endoscopic cauterization, treatment for anemia, or transfusion. Late injuries are usually clinically manifest within 3 to 4 years after RT and may include stricture, diminished rectal compliance, and decreasing storage capacity with resultant small/frequent bowel movements. Injury to the anal musculature can Rectal bleeding is usually self-limited, although some patients require medical management with anti-inflammatory suppositories, antibiotics, endoscopic coagulative therapies, or rarely surgical diversion. In patients with endoscopic rectal abnormalities after RT, the most likely diagnosis is RT effect, and biopsy should not be performed because this may lead to chronic infection, poor healing or ulceration.Radiation Therapy Oncology Group (RTOG) scoring criteria are commonly used to report toxicity (2). The original system was criticized as being vague, nonquantitative, and unvalidated. It emphasizes rectal bleeding and stool frequency but not fecal incontinence or bowel urgency, both of which impact QOL. Because of its objectivity, the presence of any rectal bleeding has been the sole endpoint reported in some series. Interpreting the rate of RT-induced sequelae is complicated because many symptoms are nonspecific and may be related to conditions such as hemorrhoids or irritable bowel disorders.The Common Terminology Criteria for Adverse Events version 3.0 is being used more often in prospective clinical trials (3). It provides more specific descriptions of common toxicities after cancer therapy and is more quantitative than the RTOG scoring criteria. CHALLENGES DEFINI...

Using daily diagnostic quality images to validate planning margins for prostate interfractional variations

“…This was demonstrated dosimetrically herein as the number of daily sessions receiving high rectum or bladder dose was reduced with decrease in margin. Based on previous reports, 1 , 2 , 35 rectum sparing is likely to translate into a decreased rate and level of late GI toxicity. The decrease of dose to the bladder may alleviate GU complications in the setting of standard fractionation and with prostate SBRT, which has shown higher (15.6%) late GU toxicity rate than that (12.6%) of the standard‐fractionated IMRT (36) …”

“…Daily rectal dose with an equivalent of ${\mathrm{normalV}}_{70\text{Gy}}>30\%$,$>25\%$,$>20\%$, and$>10\%$ was analyzed. ${\mathrm{normalV}}_{70\text{Gy}}>20\%$ has been consistently associated with rectal bleeding or Grade ≥ 2 late rectal toxicity (1) . The endpoint of bladder was chosen as ${\mathrm{normalV}}_{65\text{Gy}}$.…”

“…A large PTV expansion adversely affects the radiation dose to the nearby organs at risk (OAR). Data from multiple centers associate high rectum and bladder doses with higher incidences of late toxicities (1) . A meta‐analysis of over 10,000 patients treated using IMRT for prostate cancer showed a grade 2 or above late gastrointestinal (GI) toxicity of 15% and genitourinary (GU) toxicity of 17% (2) .…”

Variations in dosimetric distribution and plan complexity with collimator angles in hypofractionated volumetric arc radiotherapy for treating prostate cancer

“…Because of intermediate‐ and low‐dose spillage caused by MLC rotation, intermediate‐ and low‐dose areas were predominant in the rectum. According to parameters of the Lyman–Kutcher–Burman normal tissue complication probability model from four clinical series, Michaslski suggested that high doses are crucial for determining the risk of rectal toxicity 24. Thus, we can infer that MLC rotation does not increase the risk of late rectal toxicity.…”

Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer

“…The term gEUD is the generalized equivalent uniform dose which accounts for the fact that the rectum does not receive a uniform dose during treatment and is calculated according to the Kutcher–Burman histogram dose reduction method,32 $gEUD={\left(\frac{1}{N_{voxels}},\underset{i=1}{\overset{N_{voxels}}{false\sum }},D_i^{1/n}\right)}^n,$where N voxels is the number of voxels, D i is the dose to the i th voxel, and n is the volume effect factor, which models how the tolerance dose changes as the fractional volume of the rectum irradiated changes. To evaluate a minimum of grade 2 rectal toxicity, QUANTEC‐recommended parameters were used 33. They are as follows: n  = 0.09 (0.04 – 0.14), m  = 0.13 (0.1 – 0.17), and TD 50  = 76.9 Gy (73.7 – 80.1).…”