ACRIN and RTOG® release the results of the first multicenter trial to demonstrate the potential of PET imaging to predict long-term prognosis.
Recently reported clinical trial results suggest an important link between patient prognosis and [18F] fluorodeoxyglucose positron emission tomography (FDG-PET).
Conducted by investigators within ACRIN and the Radiation Therapy Oncology Group (RTOG®), the collaborative trial was undertaken specifically to see if FDG-PET could determine the status of inoperable non-small cell lung cancer (NSCLC) following initial treatment. If so, FDG-PET could help identify patients who would benefit from more intense treatment and provide early assessment of the efficacy of new combined-modality treatment. Validating FDG-PET for this purpose could be especially helpful because the inflammatory effects of radiation on the lung and other tissues can make post-treatment chest CT images (currently the most common post-treatment imaging exam) difficult to read.
The investigators of the trial (ACRIN 6668/RTOG 0235) found that the higher the standardized uptake value (SUV) — a measure of how rapidly tumor cells are using the glucose-based FDG radiotracer — acquired from a FDG-PET scan shortly after chemoradiation treatment, the worse the patient outcome. "The results show us that FDG-PET can help determine which patients have the most aggressive tumors," explains Mitchell Machtay, MD, the study's principal investigator and lead author. "However, more investigation is needed before we can use this information for definitive clinical decision making," he says. Machtay is also RTOG deputy chair and chair of radiation oncology at UH Case Medical Center and Case Western Reserve University School of Medicine in Cleveland.
Approximately 250 patients with inoperable stage III NSCLC were enrolled in the study at 37 US-based institutions. Patients received conventional concurrent platinum-based chemotherapy and radiotherapy, and a post-treatment FDG-PET scan was performed approximately 14 weeks after treatment. Based upon the results of previous small, single-institution studies, the investigators pre-established a cutoff SUV of 3.5 as a prognostic indicator of a patient's outcome. In other words, patients with an SUV less than or equal to 3.5 would do significantly better than patients with a value above 3.5. One important finding during the study was that the cutoff SUV point of 3.5 is not associated with survival. Additionally, when the SUVs were analyzed using both "peak SUV" and "maximum SUV" techniques, study results did not differ greatly.
Determining an appropriate SUV cutoff point may be only part of the story.
"Although we did not find that an SUV cutoff point of 3.5 provides prognostic information as hypothesized, several exploratory analyses did not provide interesting results," says Machtay. For example, they found that no patient with an SUV over 7.0 survived more than two years. The authors also investigated other cutoff points for correlation with survival and found that an SUV of 5.0 could have potential clinical value. However, Machtay emphasizes that the use of the 5.0 cutoff requires additional validation.
Determining an appropriate SUV cutoff point may be only part of the story, notes the trial's nuclear medicine co-chair, Barry A. Siegel, MD, FACR, ACRIN co-deputy chair, chief of the Division of Nuclear Medicine at Mallinckrodt Institute of Radiology, and professor of radiology and medicine at Washington University of Medicine in St. Louis. "We may find that metrics other than SUV, or in combination with SUV, provide more definitive prognostic information. Several promising techniques are under investigation, including evaluating FDG-PET during radiotherapy before radiation pneumonitis occurs and using alternative radiotracers, such as FMISO, for the detection of hypoxia," he says.
Both of these approaches are being studied in the recently launched RTOG 1106/ACRIN 6697 trial (see sidebar) with a patient population similar to that enrolled in the ACRIN 6668/RTOG 0235 trial. This is the first trial to test whether using information obtained from FDG-PET/CT scans during treatment to adapt radiotherapy to the individual patient's tumor during the course of treatment can improve local tumor control. "What's exciting about this study is the incorporation of a PET scan early — after just four weeks of chemoradiation — which allows adjustments to the radiation therapy treatment. The idea is to perform the scan after the tumor has begun to shrink and yet before there's too much inflammation, so that the dose delivered to the remaining tumor can be intensified," explains Machtay.
By Nancy Fredericks, MBA