Radiation delivery for cancer treatment has undergone a huge technologic revolution. Progression from two-dimensional (2D) to three-dimensional (3D) treatment planning was the first major shift, allowing for conformal radiation therapy. We now routinely use highly conformal intensity modulated radiation therapy (IMRT), along with image guided radiation therapy (IGRT), in the leading-edge centres. These technologies allow us to deliver higher radiation doses to the tumour (for better cancer control) with fewer side effects (by sparing surrounding normal tissues such as the rectum and bladder).
This article describes the current state of our technologic capabilities in radiation oncology with respect to prostate cancer treatment. Although permanent radiation seed implantation and high dose rate brachytherapy are also options for patients, this report focuses on external beam radiation. (A mini-glossary on page 7 should help you understand some of the highlighted technical terms.)
Steps along the way
Radiation delivery was initially based on marks placed on the patient’s skin. The physician used his knowledge of surface anatomy to guide the treatment beams — hardly high-precision therapy. The introduction of plain x-rays in the process, referred to as 2D treatment planning, helped to better guide the beams. The target location was estimated using bony landmarks (soft tissues such as the prostate cannot be seen with plain x-rays, because all the surrounding organs and muscles have a similar x-ray density).
The emergence of computerized tomography (CT) brought two advantages: it allowed physicians to see the soft tissues, and it gave us a series of cross-sectional slices through the body that provided a 3D picture. As CT entered mainstream radiation medicine, we were able to identify the actual tumour and surrounding organs, and plan the radiation with the goal to treat the target while minimizing the impact of radiation on nearby tissues (e.g. rectum, bladder). Less dose to a smaller volume of surrounding normal tissues means fewer side effects.
With 2D planning, a small number (two to four) of simple rectangular fields were used. The field could be shaped using custom-designed, heavy blocks that had to be manually inserted into the treatment beam (a different set of blocks for each field) but this was expensive, slow and arduous work. Ultimately, the design of treatment machines evolved to incorporate electronically controlled blocking mechanisms called multileaf collimators that allowed for more efficient delivery of radiation (the beam can be shaped and moved to treat the tumour from different angles). 3D conformal radiation therapy (3DCRT) now uses four to six fields of radiation, each potentially outlined by multileaf collimators.
Initially, we had to calculate by hand the distribution of the dose across one or more radiation beams, and how it would vary as it travelled through the tissues of the body. This took hours of work and limited us to one or two fields with minimal beam shaping. As computers and software replaced these hand calculations, they helped to increase our confidence in using more sophisticated beam arrangements and shaping.
IMRT was the next technologic advance in the conformal approach. Now, instead of having the same intensity across the opening of each field, the machine (and planning systems) can vary the intensity of beam across each field. This has given us unprecedented ability to control or “sculpt” the radiation dose, maintaining good coverage to the target but with less exposure to normal tissues.
In the latest development, IGRT, the target is imaged just prior to radiation delivery, while the patient is lying in the treatment position. The addition of a cone-beam CT onto the linear accelerator (IGRT unit) has permitted sophisticated 3D image guidance of a small, defined area — in this case the prostate. Photos on page 5 and 7 illustrate two linear accelerators that allow for IGRT-IMRT, now in routine use for prostate cancer patients at the Odette Cancer Centre.
3D conventional versus IMRT
The figure below opposite illustrates IMRT (left) and 3D conventional (right) dose distributions for a patient with intermediate-risk prostate cancer given a prescribed dose of 7800 centi-Gray (cGy) — the standard amount used at the University of Toronto — in 39 treatment fractions. The aim is to cover the prostate and margin by approximately the 7800 cGy isodose line. This IMRT plan is generated based on seven intensity modulated fields, and the conventional approach on four non-intensity modulated fields. The figure shows the high-dose isodose lines (7800 [yellow], 7400 [white], 7000 [light green] cGy) conforming more tightly around the prostate gland (red colour wash) with safety margin (green colour wash), while sparing more of
the rectum (brown contour). The lower dose isodose lines (5000 [forest green] and 4000 [purple] cGy) illustrate less exposure to normal tissue with the IMRT, compared to the four-field conventional distribution.
One randomized controlled trial (RCT; the type of research study considered to be the most reliable), in which 225 men received either conventional or conformal radiation, reported significant results. The incidence of radiation-induced proctitis and bleeding was 5% for conformal, compared to 15% for conventional, radiation.
The evolution of technology has made it possible to investigate doses beyond the traditional 6400–7000 cGy range. Also, as we’re able to spare normal tissues more effectively using IMRT, we can now safely explore giving prostate cancer patients the same or a greater radiation dose in a shorter overall treatment time (called hypofractionation).
PSA control
Several prostate cancer RCTs have tried to find out whether raising doses with external beam radiation would translate into improved outcomes. Four out of seven recent studies reported a significant difference in PSA control rates, ranging from:
- a 10% advantage with the addition of 1000 cGy (for patients receiving 3DCRT)
- an improvement of 19% when the dose was increased by 900 cGy (patients had 3DCRT up to 5040 cGy, then an additional radiation “boost” delivered by proton therapy)
- a 19% benefit with the addition of 800 cGy (2008 updated results of the landmark M.D. Anderson Cancer Center dose escalation study)
- an improvement in biochemical control of 11% on a 1000 Gy increase in total dose
In the first prostate dose escalation RCT reported in 1995, all patients had advanced high-risk disease and received 5040 cGy by 2D fields followed by a conformal proton therapy boost. Adding 800 cGy improved local control by 8%, but this difference wasn’t considered statistically significant (reliable). The study was also done prior to PSA, so the results aren’t comparable to those from the other studies.
Similar RCTs comparing hypofractionated radiation to the standard at the time noted no significant difference in biochemical control, which suggests that it’s safe to increase the dose per fraction in order to cut treatment time for the patient.
The current PROFIT trial of modern radiotherapy (by the Ontario Clinical Oncology Group) comparing 7800 cGy in eight weeks with 6000 cGy in four weeks will reveal whether shorter, more intense treatment is equivalent to the standard (or even an improvement) in terms of PSA control. This study is important, as it’s often difficult for patients to commit to daily trips to the cancer centre for eight weeks. If treatment can be reduced to four weeks with the same efficacy and toxicity, then both the patient and the healthcare system will benefit.
High dose = more side effects?
Research indicates that the risk of late toxicity to both the rectum and bladder requiring medical intervention is low — between 5% and 10%. And, with modern radiation planning techniques, it doesn’t seem likely that increasing the dose would add to the risk of serious complications. Some gastrointestinal and genitourinary side effects do occur, however, and have an effect on patients’ lives. As we learn more about the amount of radiation the rectum, bladder and small bowel can safely tolerate, and improve the ability to avoid radiation to the organs surrounding the prostate, we hope to reduce these side effects even more.
More progress to come
So do modern radiotherapy techniques really deliver? Based on the evidence, they allow for higher doses of radiation, lead to better PSA control, and involve a low risk of side effects. As the field continues to evolve, we hope to use these new technologic advances to further improve outcome and benefit to patients — the ultimate treatment goal.
Dr. Arjun Sahgal is a Radiation Oncologist at the Odette Cancer Centre, Sunnybrook Health Sciences Centre, and Assistant Professor at the University of Toronto (Ontario).
Elizabeth Lui, MRT (T), CMD, is a certified medical radiation technologist at the Odette Cancer Centre.
Dr. Andrew Loblaw is a Radiation Oncologist at the Odette Cancer Centre, and Associate Professor at the University of Toronto.
