Current Status and Future Potential of Advanced Technologies in Radiation Oncology
Part 2. State of the Science by Anatomic Site

On November 30–December 2, 2006, the Radiation Research Program of the Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI) hosted a workshop entitled “Advanced Technologies in Radiation Oncology: Evaluating the Current Status and Future Potential of Proton and Other Heavy Charged-Particle Radiation Therapy, Intensity Modulated Radiation Therapy and Stereotactic Radiation Therapy.” In last month’s issue of ONCOLOGY, we provided a general overview of the workshop discussion, focusing on the challenges posed by the new technologies and resources available or in development for meeting those challenges. In part 2 of this report, we will outline the more specific data discussed regarding radiation therapy for different anatomic sites.

Objectives
One of the objectives of this meeting was to define the current state of the science for various disease sites, to include two major considerations:

• The rates of tumor control and toxicity following “traditional” conformal radiation therapy for some common cancers

• An examination of the evidence from phase III studies that the advanced technologies helped patients live longer and/or better (with a better quality of life).

In many instances, data in support of the latter are not yet available. The workshop participants did not interpret this as a negative, but rather an opportunity and a need for undertaking clinical trials. Indeed, an overarching conclusion was that we need robust quality assurance procedures for these advanced technologies that would, in turn, facilitate robust clinical trials. The need for incorporating quality-of-life measures, such as patient-reported outcomes and quality-adjusted life years, was emphasized. Some participants also underscored the need for exercising caution in employing these technologies outside of clinical trials at present.

This workshop report is not, however, intended to be an exhaustive review of the field. Many single-institution reports that have suggested benefit from the advanced technologies are not included herein.

Limitations of Traditional Radiation Therapy

Table 1 summarizes the outcomes after conventional radiation therapy for several kinds of cancers, in terms of both tumor control and adverse effects.[2-25] While not an exhaustive list, it does illustrate—based on clinical trials that helped establish the standards of care for many common cancers—how much room there is for improvement. It also highlights what the authors of those trials reported as the most problematic adverse effects.

Evidence of Superiority of Advanced Technologies

For several disease settings—including head and neck, laryngeal, non–small-cell and small-cell lung, esophageal, pancreatic, cervical, endometrial, rectal, and anal cancers, breast cancer treated by mastectomy, and early, resected, and locally advanced intermediate-risk prostate cancer—no evidence of superiority has yet been shown for the advanced technologies in prospective randomized trials. In the following settings, some comparisons can be drawn regarding the available data for traditional and advanced radiation therapy techniques.

Single Brain Metastasis
In one arm of a prospective randomized trial,[1] traditional radiation therapy to the whole brain was delivered in 94 patients suffering from cancer and a single metastasis to the brain, between 1996 and 2001. Following the treatment, 50% of patients died within 4.9 months, and almost all died within 2 years. Local failure was observed in 29% of the treated lesions within 1 year.

Acute toxicity of grade 3 or 4 was not observed in any patient, but grade 3/4 late toxicities (occurring at or beyond 90 days) developed in 3% of patients after receiving traditional whole-brain radiation therapy. The most common side effects were nausea/vomiting, hearing loss, and central neurologic effects.

• Stereotactic Radiation Therapy—On another arm of that prospective randomized trial, 92 patients received boost irradiation by focal stereotactic radiation therapy in addition to traditional whole-brain radiation therapy. Following treatment, 50% of those patients died within 6.5 months (this duration was 1.6 months longer than in those treated without stereotactic radiation therapy, P = .039). Local failure was observed in 18% of the treated lesions within 1 year (this rate was 11% lower than in those treated without stereotactic radiation therapy, P = .01).

Acute grade 3/4 toxicities were observed in 3% (vs none among those treated without stereotactic radiation therapy), and late grade 3/4 toxicities in 6% (vs 3% without stereotactic radiation therapy) of patients receiving stereotactic radiation therapy. The early and late toxicities were, thus, slightly worse with the latter treatment but did not differ greatly between the two arms.