Rectal toxicity includes diarrhea, loose stools, tenesmus, proctitis and urgency. The most common late toxicity is bleeding. Ulceration and fistula are far less common. The anus is at risk for fibrosis, stricture and incontinences.
The rectum extends from the anal verge (ischial tuborosities) to the rectosigmoid junction. There is uncertainty in the inferior and superior borders on CT imaging with variable cranial and caudal extents. The rectum is also mobile and distensible with significant differences depending in filling and also on bladder filling. Rectal position varies both during a fraction and between fractions. The percentage of rectal wall in the field is subjective and varies. William Beaumont Hospital demonstrated that rectal volume and rectal wall V50 to V70 values were predictive of late toxicity. The rectal wall dose being more predictive of late effects and acute toxicity predictive of late effects.
The percentage of the rectum and rectal wall receiving a given dose is subjective and variable. This can be somewhat compensated by using the actual volume of rectal wall receiving radiation. William Beaumont demonstrated rectal absolute volume as wellas rectal wall V50 to V70 were predictive of late toxicity. The rectal wall was more predictive of Grade 2 - 3 late effects. (Grade 2 - 3 RTOG increased bowel movements up to 7 -9 /day, severe cramping RTOG CGCTC).
MSKCC reviewed dose escalated prostate cancer treatments and found the percent of rectum receiving 62% to 102% of the prescribed dose of 70 - 76 Gy had significant prognostic implications in rectal toxicity.
MDACC looked at rectal toxicity in a trial of dose escalation 70 Gy v. 78 Gy for early to intermediate risk prostate cancer. The risk of grade 2 or higher late rectal toxicity was signficantly higher when V70 was ≥ 25% at 46% compared with < 25% at 16%. MDACC retrospectively compared dose-volumes and found that risk was a continuous function of dose and volume. They suggested the following cut-off points:
They found that the risk of grade 2 or higher complications was 54% with a V70 > 26% and 13% for those beolow 26%.
William Beaumont found a significantly increased risk of grade 2 or higher rectal toxicity if the rectal or rectal wall volume exceeded 15 ml.
Gynecologic studies of cervical cancer treated with intracavitary brachytherapy historically have found a < 4% toxicity with doses < 80 Gy to point A. The incidence rises to 13% for Point A dose ≥ 95 Gy.
University of Chicago and RTOG examined medical history risk factors ad adjuvant factors to rectal dose and volumes and found toxicity was also a function of
Given the toxicity is a function of dose and volume [p(Toxicity) = f(dose, volume, patient factors)], the following dose and volume constraints are recommended:
Bladder injury can result in bleeding or fibrosis and reduced distensibility. Acute effects include frequency, urgency and dysuria. Late effects include dysuria, frequency, urgency, contracture, spasm, decreased flow and incontinence. If there is focal bladder injury, late effects may manifest as hematuria, fistula, obstruction and necrosis.
The bladder is highly variable with constant filling and variable emptying. This poses technical challenges for calculating the bladder dose, but also opportunities for minimizing bladder dose (or maximizing bladder dose, when required). Accurate dose-volume relationships are much more difficult to quantify due to this variable size nature of the bladder.
Detailed dose — volume relationships have not been published. Whole bladder doses and toxicities have been obtained from bladder cancer patients. Partial bladder data is obtained from mainly prostate cancer irradiation or gynecologic irradiation.
Whole bladder doses in excess of 60 Gy with fraction sizes > 2 Gy or hyperfractionated/accelerated treatments result in significantly increased risk of Grade 3 or higher toxicity. Risk is lower when the whole bladder dose is kept to 45 - 55 Gy with a partial bladder boost to > 60 Gy. Smaller areas of higher doses used in prostate cancer treatment seem to be well tolerated with abutting (inferior) regions tolerating > 70 Gy in the trigone area. Other factors that affect dose-volume tolerance include prior pelvic surgery anticoagulation (hematuria), cytoxan (hemorrhagic cystitis), incontinence, contractures, and vesicoureteral reflux. Radiation sensitizing chemotherapy may increase the risk of acute and late bladder toxicity, but this has not been demonstrated with data.
Whole bladder radiation to 50 to 60 Gy reported toxicity risks range from ≤ 5% to 40%. This range is likely due to the changeable nature of the bladder in the pre-IGRT imaging days.
Specific recommendations for bladder constraints are: