Summary of Evidence
Breast Cancer
For individuals with breast cancer who receive interim FDG-PET as an adjunct to interim CT , the evidence consists of several systematic reviews, two (2) RCTs, long-term results from one (1) of the two (2) RCTs, and many observational studies. Relevant outcomes are OS , disease-specific survival, change in disease status, QOL , morbid events, and treatment-related morbidity. Results from systematic reviews have shown wide ranges in sensitivities, specificities, PPVs, and NPVs. The wide ranges might be due to small sample sizes, the use of various definitions of the outcome measure (pathologic complete response), and differences in breast cancer subtype populations. Two (2) RCTs were identified in which therapy decisions were guided by FDG-PET results. In the first RCT, nonresponders, determined by PET measures, were given more intensive chemotherapy. Although the results showed initially higher response rates in the more intensive treatment group, this did not translate to long-term improvements in disease-free survival. The second RCT found that individuals receiving less intensive initial treatment who were determined to be responders by PET measures had significantly higher response rates to treatment; however, three (3)-year disease-free survival results have not yet been published. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
Esophageal Cancer
For individuals with esophageal cancer who receive interim FDG-PET as an adjunct to interim CT, the evidence includes two (2) meta-analyses, two (2) nonrandomized studies, and two (2) retrospective studies. Relevant outcomes are OS, disease-specific survival, change in disease status, QOL, morbid events, and treatment-related morbidity. Results on clinical validity were inconsistent across the studies. The meta-analysis reported low pooled sensitivities and specificities, while a subgroup analysis including only individuals with squamous cell carcinoma and two (2) studies published after the meta-analysis reported an adequate potential in predicting responders to neoadjuvant therapy. No evidence was identified that examined the clinical utility of PET for individuals with esophageal cancer. Evidence for clinical utility of FDG-PET for individuals with esophageal cancer consists of one (1) meta-analysis and 1 RCT. The meta-analysis found that individuals considered to be responders early in therapy based on FDG-PET assessment were found to have improvements in PFS and OS compared to nonresponders. A single RCT found that PET-guided therapy led to improvements in PFS, but not OS, in individuals considered nonresponders to initial therapy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
Gastrointestinal Stromal Tumors
For individuals with gastrointestinal stromal tumors receiving palliative or adjuvant therapy who receive interim FDG-PET as an adjunct to interim CT, the evidence includes a systematic review. Relevant outcomes are OS, disease-specific survival, change in disease status, QOL, morbid events, and treatment-related morbidity. The systematic review included 19 studies, two (2) of which reviewed FDG-PET scans more than six (6) months after the start of treatment. CT is currently recommended for standard long-term follow-up and surveillance of gastrointestinal stromal tumors. FDG-PET is equivalent to CT in the detection of treatment response when follow-up is long-term. No studies were identified that tested outcomes following PET-guided treatment. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
For individuals with gastrointestinal stromal tumors treated with TKIs for six (6) months or less who receive interim FDG-PET as an adjunct to interim CT, the evidence includes a systematic review. Relevant outcomes are OS, disease-specific survival, change in disease status, QOL, morbid events, and treatment-related morbidity. The systematic review included 19 studies, 17 of which showed that FDG-PET detected an early response to tyrosine kinase inhibitor therapy, which was a strong predictor of clinical outcomes. FDG-PET detected treatment response as early as one (1) week after initiation of treatment. While CT detects anatomic changes in the tumor, PET detects changes in the metabolic activity of the tumor. Because metabolic changes precede anatomic changes by several weeks or sometimes months, PET can detect treatment response earlier than CT. PET is therefore preferred if a rapid read-out of response to targeted therapy is needed to guide treatment decisions (e.g., change in targeted therapy or surgery). While no studies were identified that tested outcomes following PET-guided treatment, it is possible to construct a chain of evidence demonstrating improved individual outcomes. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
Head and Neck Cancer
For individuals with head and neck cancer who receive interim FDG-PET as an adjunct to CT, the evidence includes several systematic reviews. Relevant outcomes are OS, disease-specific survival, change in disease status, QOL, morbid events, and treatment-related morbidity. There was an overlap of studies among the systematic reviews. Most studies included in the reviews showed that FDG-PET used during radiotherapy, with or without chemotherapy, can adequately predict disease-free and OS. Meta-analyses to determine response could not be performed in any of the systematic reviews due to the heterogeneity in the methods across the studies. Most studies used maximum standardized uptake volume, however, threshold values to determine response varied across studies. No studies were identified that provided evidence for the clinical utility of PET. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
Lymphoma
For individuals with lymphoma who receive interim FDG-PET as an adjunct to interim CT, the evidence includes systematic reviews with meta-analyses and RCTs. Relevant outcomes are OS, disease-specific survival, change in disease status, QOL, morbid events, and treatment-related morbidity. The systematic review evaluating the validity of interim FDG-PET showed high false-positive rates for both Hodgkin and non-Hodgkin lymphomas. After the systematic review, two (2) studies were published; one (1) focused on individuals with follicular lymphoma and the other on individuals with T-lymphoblastic leukemia/lymphoma. These studies showed a potential for FDG-PET to predict survival rates for these specific lymphomas. Evidence for the clinical utility of interim PET for guiding treatment in individuals with lymphoma consists of two (2) Cochrane reviews and several RCTs. One Cochrane review reported lower PFS in individuals receiving PET-guided therapy compared with individuals receiving standard care. Another Cochrane review found moderate-certainty evidence that interim PET scan results predict OS, and very low-certainty evidence that interim PET scan results predict PFS in treated individuals with Hodgkin lymphoma. The RCTs that compared PET-guided therapy with standard therapy did not demonstrate noninferiority. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
Non-Small-Cell Lung Cancer
For individuals with NSCLC who receive interim FDG-PET as an adjunct to interim CT, the evidence includes numerous small observational studies. Relevant outcomes are OS, disease-specific survival, change in disease status, QOL, morbid events, and treatment-related morbidity. While most studies showed correlations between FDG-PET measurements and progression-free and OS, the generalizability of the results is limited. The studies were small, with most population sizes fewer than 50 individuals. The studies were also heterogeneous, including individuals at different stages of the disease, undergoing different treatment regimens, and receiving PET at different times during treatment cycles. No studies were identified that evaluated outcomes after PET-guided therapy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
Ovarian Cancer
For individuals with ovarian cancer who receive interim FDG-PET as an adjunct to interim CT, the evidence includes a systematic review. Relevant outcomes are OS, disease-specific survival, change in disease status, QOL, morbid events, and treatment-related morbidity. The systematic review identified nine (9) studies that calculated hazard ratios for various FDG-PET parameters (e.g., SUVmax, MTV, tumor lesion glycolysis). The only parameter consistently showing prognostic value was tumor lesion glycolysis. Additionally, no studies were identified that evaluated outcomes after PET-guided therapy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
Other Cancers
For individuals with other malignant solid tumors (e.g., bladder, colorectal, prostate, thyroid) who receive FDG-PET as an adjunct to interim CT, the evidence includes a systematic review, NCCN task force report, and single-arm observational studies published after the task force report. Relevant outcomes are OS, disease-specific survival, change in disease status, QOL, morbid events, and treatment-related morbidity. Results have been inconsistent on the use of interim FDG-PET among the various cancers. While some have reported associations between interim FDG-PET and recurrence or survival, there is a lack of comparative trials evaluating outcomes in individuals whose treatments were altered based on PET measurements. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
