CHICAGO—A shorter, cheaper, and more convenient three- to five-week course of radiation appears to work as well or better than the traditional six- to eight-week schedule for some patients with prostate and breast cancer, according to three studies presented here at the American Society for Radiation Oncology (ASTRO) Annual Meeting.
Giorgio Arcangeli, MD, a radiation oncologist at the Regina Elena National Cancer Institute in Rome, Italy, who headed one of the prostate cancer studies, explained that although recent improvements in radiation delivery techniques made it possible to increase the radiation dose given to cancer patients and to increase cure rates, the increase in total dose was obtained by increasing the number of treatment sessions to six, seven, or even eight weeks, which, of course, adds to inconvenience and cost.
Hypofractionated radiotherapy, though, offers a more convenient alternative, delivering higher doses of radiation in fewer treatments than conventional radiotherapy.
In Dr. Arcangeli's study, high-risk prostate cancer patients who received the shorter treatment course were significantly less likely to suffer a biochemical recurrence at three years than patients who underwent conventional treatment.
A second study, led by Alan Pollack, MD, PhD, Chair of Radiation Oncology at the University of Miami, showed no significant difference in five-year biochemical recurrence rates in men with intermediate- and high-risk prostate cancer randomized to receive hypofractionated or standard radiotherapy.
In the third, single-arm, study, none of the first 121 women with early-stage breast cancer treated with a hypofractionated radiotherapy technique has suffered a local recurrence during the first two-and-one-half years of follow-up.
Importantly, hypofractionation was not associated with a significant increase in toxicity in any of the trials, all the researchers said.
High-Risk Prostate Cancer
From 2003 to 2007, Dr. Arcangeli and colleagues randomly assigned 168 men with high-risk prostate cancer to hypofractionated radiotherapy or conventional fractionation radiotherapy.
The hypofractionated approach consisted of 62 Gy in 20 fractions over five weeks, while conventional radiotherapy was 80 Gy in 40 fractions over eight weeks.
Three-dimensional conformal radiation therapy was used in both arms of the study, and all patients also received androgen- deprivation therapy for nine months.
Eligibility criteria included being under age 80 and having histologically proven prostate adenocarcinoma with a PSA level above 20 ng/mL, a Gleason score higher than 7, or Stage T3 disease or higher. Pa tients who had two of the following three factors that placed them at high risk of recurrence were also eligible: a Gleason score of 7, a PSA level of 11 to 20 ng/mL, and Stage T2c disease.
At three years, the freedom from biochemical failure rate was 87% in the hypofractionated arm, compared with 79% in the conventional radiotherapy groups, a significant difference, Dr. Arcangeli reported.
“Hypofractionated radiation not only improves the control of prostate cancer, but also offers convenience to patients by halving the number of visits to radiotherapy departments. This is an important benefit for these high-risk patients, who are typically an older, less mobile group,” he said.
None of the patients suffered acute Grade 4 adverse effects, and only one patient had an acute Grade 3 toxicity, he said.
As far as late side effects, no difference was observed between the two groups. At three years, Grade 2 gastrointestinal side effects were observed in 17% and 16% of the hypofractionated and conventional radiation groups, respectively.
The rates of Grade 2 genitourinary complications were 14% and 11% in the hypofractionated and conventional fractionation groups, respectively.
Dr. Pollack and colleagues studied 303 men with intermediate- to high-risk prostate cancer.
The men were randomly assigned to hypofractionated intensity-modulated radiotherapy involving 26 treatments over 5.1 weeks or standard intensity-modulated radiotherapy involving 38 treatments over 7.5 weeks.
Men in the hypofractionation arm received 2.7 Gy per treatment, for a total of 70.2 Gy, but the biologic equivalent of a total of 84.4 Gy, he said. Those in the standard radiation arm received 2.0 Gy per treatment, for a total dose of 76 Gy.
Thirty-four intermediate-risk patients received short-term androgen-deprivation therapy for a median of four months, and 102 high-risk patients received long-term anti-hormone therapy for a median of 24.5 months.
At a median follow-up time of 39 months, 14% of patients in the hypofractionation arm experienced a biochemical recurrence rate vs 19% in the standard radiotherapy arm, a difference that was not statistically significant, Dr. Pollack said.
“Control rates were quite high using either approach—about 85% in both groups,” he said.
As for adverse effects, Grade 2 or higher gastrointestinal toxicity was seen in 6% and 8% of the hypofractionation and standard radiation arms, respectively, and Grade 2 or high genitourinary toxicity occurred in 25% and 17%. Neither of the differences reached statistical significance.
“In this interim analysis, the shorter course of treatment appears to be as effective and as safe as the longer standard radiation course; however, longer follow-up is needed,” Dr. Pollack said.
Asked how long the patients must be followed before any recommendations can be made, he said that “over 60 patients need to fail biochemically before the final analysis, which could happen by 2011.”
In the single-arm breast cancer study, a three-week course of hypofractionation therapy cut the duration of radiation treatment in half, said chief investigator Manjeet Chadha, MD, Associate Chairman of Radiation Oncology at Albert Einstein College of Medicine and a radiation oncologist at Beth Israel Medical Center in New York City.
The approach is part of the effort to personalize care and tailor it to specific patients in specific situations, she said, noting that European and Canadian studies have already shown that a short course of radiation is just as effective as the conventional longer course for some patients with breast cancer, but that in the US there are limited data on this topic.
At the meeting, Dr. Chadha reported on the first 121 women enrolled in the ongoing trial. All had breast-conserving surgery for early-stage breast cancer, followed by the accelerated radiation treatment.
“For each patient, we developed a conformal, personalized plan using three-dimensional dosimetry data derived from the patient-specific CT images. Radiation treatment was delivered to the whole breast using an accelerated hypofractionated schedule, with the simultaneous delivery of a boost dose given to the precise location from where the tumor was removed,” she said.
So far, the women have been followed for a median of 2.3 years, with a range of 0.5 to 5.4 years, and no local failures have been observed.
None of the women experienced serious side effects—just the skin irritation, fatigue, and mild to moderate breast pain that is typical of any radiation treatment, Dr. Chadha said.”There were no acute Grade 3 or 4 toxicities observed.” A total of 68% of patients experienced acute Grade 1 skin toxicity, and four percent experienced acute Grade 2 skin toxicity.
The cosmetic results are excellent, she said, showing slides of several patients whose treated breasts looked normal at the five-year follow-up.
While the study did not include a control arm, the results obtained with the short course are what would be expected with the longer course, Dr. Chadha said.
“It is feasible to achieve an excellent dose conformity in delivering a three-week accelerated course of radiation therapy to the whole breast with concomitant breast,” she said, adding that her team plans to continue following the women.
If further study in larger numbers of women “proves this shorter schedule is effective and safe, we have an opportunity to improve the quality of life of patients.”
Commenting on the studies, ASTRO President Anthony L. Zietman, MD, the Jenot W. and William U. Shipley Professor of Radiation Oncology at Harvard Medical School, said that together with the Canadian and European studies, “the data all suggest that a shorter course of radiation is safe and effective.”
That said, “we've all been timid about change. Radiation has been given the same way for 70 years, and we have had a great fear about giving radiation in large doses,” Dr. Zietman continued,
That has led to longer and longer courses of treatment—as many as nine weeks in prostate cancer. “It will be a few more years before we are confident that it is as or more effective and as safe as standard radiation.”
Hypofractionation offers a host of advantages, “including less time away from work and family,” he said. “Are patients struggling to get in for eight weeks of treatment? I think they are. It's a struggle and costly.”
Dr. Arcangeli said he thinks practice could start changing more quickly in Italy. “Radiation oncologists [there] are closely watching the results,” he said.