Conformal Radiation Therapy Lowers the Risk of Radiation-Induced Proctitis Compa
Conformal Radiation Therapy Lowers the Risk of Radiation-Induced Proctitis Compared to Conventional Prostate Radiation Therapy
abstract & commentary
Synopsis: Late toxic effects of radiation therapy on normal tissues limit the amount of radiation therapy that can be safely administered. The development of novel methods employing multileaf collimators, three-dimensional simulation, and specially shaped blocks is called conformal radiation therapy and has the potential to more accurately deliver radiation to the tumor volume. Men were randomly assigned to receive 64 Gy in daily 2 Gy fractions to treat prostate cancer by either conventional treatment planning or conformal techniques. Those receiving conformal radiation therapy had similar disease control but significantly lower rates of radiation-induced proctitis and bleeding.
Source: Dearnaley DP, et al. Lancet 1999;353:267-272.
A major factor that limits the efficacy of radiation therapy is the limit of normal tissue tolerance to external beam radiation therapy. Thus, administration of more than 60 Gy to pelvic organs can produce a serious risk of radiation-induced proctitis, rectal bleeding, and urinary bladder problems. Some data suggest that the ability to augment the dose of prostate radiation therapy to 75 Gy might result in significantly better local tumor control than 60 Gy.1 Preliminary single-arm clinical trials suggest that the use of three-dimensional treatment planning with computed tomography, together with multileaf collimators to shape the beam and specially shaped blocks to restrict the radiation to the tumor bed, is capable of permitting the delivery of higher and more effective doses of radiation therapy and improving treatment outcome.2,3
Researchers at the Royal Marsden Hospital in the United Kingdom conducted a prospective randomized study in 225 men with prostate cancer. One-hundred-fourteen men were assigned to receive conformal radiation therapy and one-hundred-eleven were assigned to receive conventional radiation therapy. All patients had prostate cancer without lymph node involvement and had a projected life expectancy of 5-10 years. Median follow-up was 3.6 years. Patients were treated with a three field technique, anterior and lateral, or posterior oblique fields.
Those receiving conventional radiation therapy had routine treatment planning; those receiving conformal therapy had special blocks designed to shield normal tissue with a margin around the tumor field of 6 mm. Six to 10 MeV photons were the source of radiation therapy and treatment was given in 2 Gy fractions to a total dose of 60-64 Gy. By using conformal techniques, it had previously been projected that 48% less rectum and 38% less bladder would be treated to the 90% isodose.4
Baseline characteristics of the two groups were similar. Proctitis of grade 1 severity or higher occurred in 56% of patients receiving conventional radiation therapy and in 37% of those receiving conformal radiation therapy (P = 0.004). Rectal bleeding occurred in 12% of patients receiving conventional radiation therapy and in 3% of those receiving conformal radiation therapy. After five years, the actuarial probability of remaining free of grade 2 or higher proctitis was 82% in the group treated with conventional radiation therapy and 92% in the group treated with conformal radiation therapy (P = 0.002). By contrast, there were no differences between the groups in urinary symptoms.
Although the lower volume of tissue treated with radiation therapy in the group receiving conformal radiation therapy resulted in less rectal toxicity, the local tumor control rates were similar with the two approaches. Local control at two years (97% for conformal, 96% for conventional) and at five years (78% for conformal, 83% for conventional) was similar in the two groups and overall survival at five years was 66% for those on the conformal arm and 64% on the conventional arm.
Using prostate-specific antigen levels as a measure of disease control, patients on the conformal arm appeared to have somewhat better biochemical cancer control (39% at 5 years vs 31% at 5 years). However, these apparent differences did not translate into better survival.
Commentary
The treatment of prostate cancer is controversial. Not only is it not clear that all prostate cancers require treatment, there is no consensus on the best treatment approach to those that do require treatment. Radical prostatectomy is generally considered to be the treatment of choice, but a large fraction of patients become impotent as a consequence of the treatment and a small, but significant, fraction of patients become incontinent as well. Radiation therapy has generally been felt to be inferior to surgery because it is also associated with serious toxicities to the bladder and rectum, serum prostate-specific antigen levels did not fall as quickly or as far as one would like to see, and some studies suggest a higher relapse rate.
The evidence is reasonably strong that the ability to safely deliver higher doses of radiation therapy to the primary tumor might improve the treatment results from radiation therapy. Using conformal techniques, it may be possible to increase the radiation doses to 78-81 Gy. Large studies are currently in progress to compare conventional treatment planning that delivers 64 Gy with conformal treatment planning that delivers 74 Gy or more. It will be of interest to know whether these higher doses of radiation therapy are capable of improving local disease control at an acceptable risk of toxicity. Ongoing randomized studies are addressing this question.
It is somewhat disappointing that the conformal treatment planning appears to be ineffectual at altering the risk of bladder toxicity. It is conceivable that the bladder could be protected by instilling a radioprotective agent into the bladder during treatment. It is also possible that brachytherapy could be designed to deliver a higher and more effective dose of radiation to the tumor.
References
1. Williams MV, et al. Int J Radiat Oncol Biol Phys 1984;10:1703-1707.
2. Zelefsky MJ, et al. Int J Radiat Oncol Biol Phys 1998;41:491-500.
3. Hanks GE, et al. Int J Radiat Oncol Biol Phys 1998;41:501-510.
4. Tait DM, et al. Radiother Oncol 1997;42:121-136.
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