Current Status and Future Potential of Advanced Technologies in Radiation Oncology
Part 2. State of the Science by Anatomic Site
By BHADRASAIN VIKRAM, MD
Clinical Radiation Oncology Branch
C. NORMAN COLEMAN, MD
Radiation Research Program
JAMES A. DEYE, PhD,
Radiation Research Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
April 14, 2009
The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
The opinions and conclusions in this report are those of the individual authors and participants and do not reflect an opinion or policy of the National Cancer Institute or the US Government.
A total of 240 patients (79%) with 5-year photographs were available for analysis. Change in breast appearance was identified in 71 of 122 patients (58%) who were allocated conventional treatment, compared to 47 of 118 patients (40%) allocated IMRT. Patients in the control arm were 1.7 times more likely to have a change in breast appearance than those in the IMRT arm, after adjustment for year of photographic assessment (95% confidence interval = 1.2–2.5; P = .008). No significant differences between the two treatment groups were found in patient-reported breast discomfort, breast hardness, or quality of life.
In another prospective randomized trial, 358 women were randomized after lumpectomy to conventional radiation therapy (using wedges) or IMRT between 2003 and 2005. It was hypothesized that 36% of patients in the control arm would suffer moderate to severe acute skin toxicity, whereas in the IMRT group, no more than 21% would. Analysis showed that 36.7% of patients in the control arm suffered such toxicity vs 27.1% in the IMRT arm. Thus, this study did not meet its primary objective. However, it was noted by the authors that among the controls, 48% developed moist desquamation vs 31% of those receiving IMRT. They also noted that women with larger breasts were more likely to suffer moist desquamation.
These two studies therefore suggest that moist desquamation in the short term (especially in large-breasted women) and a change in breast appearance in the long term are less likely among women treated by IMRT after lumpectomy. Some workshop participants objected to the use of the term “IMRT” for describing the techniques employed in those trials. They felt that—billing considerations aside—the use of multiple subfields in order to mainly improve dose heterogeneity within the target volume did not rise to the level of IMRT designed to spare the organs at risk.
As yet, no phase III trial can tell us whether the survival or local control of patients with breast cancer is better or worse, if after lumpectomy they are treated by advanced technologies instead of or in addition to traditional conformal radiation therapy.
Locally Advanced, High-Risk Prostate Cancer
In one arm of a prospective randomized trial,[19-21] traditional conformal radiation therapy (70 Gy in 35 fractions over 7 weeks) was delivered to 198 patients suffering from locally advanced prostate cancer. Following treatment, 38% of patients died within 5 years (21% due to prostate cancer). The patterns of failure revealed that 16% suffered local failure within 5 years, while 29% developed distant metastases.
On another arm of the same study, 203 patients received androgen suppression in addition to traditional conformal radiation therapy. Following treatment, 22% of patients died within 5 years (6% due to prostate cancer). The patterns of failure revealed that 2% suffered local failure, while 10% developed distant metastases.
The incidence of side effects (other than erectile dysfunction) was not different between those treated with and without androgen suppression. Fatal toxicity developed in 1% (4 patients, all of whom died due to urinary strictures). In addition, grade 3 toxicity developed in 2.7% (10 patients, including 9 with urinary strictures/toxicity and 1 with small bowel obstruction). Grade 2 toxicity developed in 19%, the most common being urinary effects (cystitis, hematuria, urinary strictures, and incontinence), proctitis, and leg edema. Erectile potency decreased in 41% of patients after treatment by radiation alone, vs 68% of patients receiving androgen suppression.
• Proton Radiotherapy—At present, no evidence from randomized clinical trials has shown that survival or side effects of patients with locally advanced prostate cancer are improved if they are treated by advanced technologies instead of or in addition to traditional conformal radiation therapy.
A prospective randomized trial[31,32] compared photon radiotherapy delivered with vs without proton radiotherapy. The investigators found no difference in survival between the two groups, but patients receiving proton radiation were more likely to suffer rectal bleeding (32% vs 12%; P = .002) and urethral strictures (19% vs 8%; P = .07). In this study, the addition of an advanced technology unexpectedly resulted in an inferior result.
The advanced technologies offer exciting and potentially substantial advantages in radiation dose distributions that may help improve patient outcomes. Many early cooperative group clinical trials involving advanced technologies primarily focused on “feasibility in the cooperative group setting” as an endpoint. We are pleased to note that since this workshop, a number of trials have incorporated specific hypotheses regarding improvements in outcomes, and some have also incorporated early stopping rules in case the outcomes prove unsatisfactory in comparison to predefined thresholds.
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