Dr Michael Farwell on FDG PET/CT Imaging to Predict Immunotherapy Response in Advanced Melanoma

Changes in melanoma metastases identified using early 18F-fluorodeoxyglucose (FDG) PET/CT scans were found potentially predictive of pembrolizumab response and had a significant correlation with progression-free survival (PFS) in a study published in Clinical Cancer Research.

The study was designed to evaluate the efficacy of the noninvasive imaging biomarker for patients with cancer receiving immunotherapy and explore the biomarker’s potential to predict treatment responses at a quicker rate than standard procedures.

Generally speaking, patients receiving immunotherapy undergo imaging around 3 months after the start of their therapy, but other investigations have been working to assess the value of conducting these scans at 6 weeks and sooner. Authors of the current study hypothesized that the use of 18F-fluorodeoxyglucose (FDG) PET/CT could detect metabolic changes in patients’ tumors after only 1 week.

In an email interview with The American Journal of Managed Care^® (AJMC^®), corresponding author Michael Farwell, MD, associate professor of radiology at the Hospital of the University of Pennsylvania, discussed the implications of the findings for the current and future skin cancer treatment landscape, how this technique can evolve, the challenges of this research, and how the findings could provide benefits beyond the scope of skin cancer.

AJMC: Can you contextualize the implications of 18F-fluorodeoxyglucose (FDG) as a noninvasive imaging biomarker in skin cancer and how this innovation advances the current treatment landscape?

MRI Machine | image credit: Alexey - stock.adobe.com

Farwell: Since this approach uses FDG PET/CT scans, which are widely available, and we are measuring changes in SUV_max, which are routinely reported in clinical reads, we expect that this approach could be readily applied to routine clinical practice to assess early response to immunotherapy. I think that early FDG PET/CT has 3 major applications:

First, it could guide patient management (“personalized medicine”) to improve outcomes by increasing response rates to immunotherapy (and survival) and/or decreasing toxicity. More specifically, responding patients could de-escalate therapy or avoid surgery, and nonresponding patients could escalate their immunotherapy regimen or change to a new therapy. Early FDG PET/CT will allow physicians to make these treatment changes at 1 week instead of at 3-6 months, and changing therapy earlier, when there is a smaller tumor burden, has the potential to increase response rates and survival.

Second, it can help us learn about immunotherapy response and tumor biology, which could help to advance the field. For example, it was very interesting to see how the kinetics of response varied both between patients and also between different lesions in the same patient—we have a lot to learn about what these differences in kinetics mean. We also need to better understand what the changes in metabolism represent with regard to both the tumor cells and immune cells.

Finally, it could serve as a biomarker in early phase 1 trials of new immunotherapies and immunotherapy combinations to help identify which therapies should advance to later stage clinical trials.

AJMC: Given the rapid pace of technological advancements in medical imaging, do you foresee any potential refinements or enhancements to FDG PET/CT imaging techniques that could further improve its sensitivity and specificity in detecting early metabolic changes in patients with skin cancer?

Farwell: Definitely! PET/CT scanner technology is continuing to advance, with improved sensitivity that yields higher quality images and allows for lower doses and/or faster scans. One example is the development of PET cameras with a much larger field of view, such as the PennPET Explorer, uEXPLORER, and Biograph Vision Quadra, which have approximately 40 times the sensitivity of current PET/CT cameras. These new PET/CT cameras will allow us to measure metabolic changes with greater sensitivity and accuracy, with a lower radiation dose to patients.

AJMC: Did you encounter any challenges throughout your study? Are there any challenges that clinicians or researchers will need to consider as research expands in this area?

The SUV (standardized uptake value) provides a quantitative measure of FDG activity, but this measure can vary between different scanners. So as this approach expands into clinical practice it will be important for patients to have their baseline and early FDG PET/CT scans performed on the same scanner, so the change in SUV between scans is accurate.

AJMC: What was the most surprising result from your study and what implications does this finding carry for future research in medical imaging, cancer detection, and affected patients?

I think that it is important to emphasize that this is the first time that anyone imaged patients with FDG PET/CT at 1 week after starting immunotherapy —so, we didn’t know what we were going to find. Thus, it was extremely exciting to see these very large changes in FDG activity, which were only seen in responding patients, and were correlated with progression-free survival. Also, we were largely expecting to see increases in FDG activity due to infiltration of tumors by activated immune cells and were surprised to see such large metabolic responses (with decreased FDG activity) at 1 week, since this implies that the immune response is happening very quickly. Additionally, we found that metastases became easier to detect on the early FDG PET/CT scan, in responding patients that had a metabolic flare, so in two cases we identified occult metastases that helped to guide clinical management (for example, an occult brain metastasis was identified and subsequently treated with radiation therapy).

These results demonstrate that there are dramatic changes that are occurring in tumors and the peripheral blood very early after starting immunotherapy. Although many clinical trials have focused on collecting data at 3 weeks and later, I think that it is important to collect imaging and blood data earlier, at 1-2 weeks, when the immune response is peaking in most patients, since this data will likely enable us to identify both responding and nonresponding patients with a high degree of confidence, and allow changes in therapy very quickly. In some cases this may also lead to improved detection of sites of metastases, at least with early FDG PET/CT, in responding patients that have a metabolic flare.

AJMC: Beyond the scope of the current study, do you believe that FDG PET/CT imaging has the potential to serve as a valuable tool for monitoring treatment response and guiding personalized therapeutic approaches in other forms of cancer? If so, what are some key areas of research that should be prioritized to further explore this potential?

Early FDG PET/CT imaging is detecting metabolic changes due to tumor infiltration by activated immune cells, as well as immune cell exhaustion and tumor cell death, which is the general mechanism by which immunotherapies generate an anti-tumor effect. Thus, early FDG PET/CT has the potential to be applied across a wide variety of other cancers and immunotherapy regimens, including cellular therapy. For example, we are planning on evaluating this approach in patients with non–small cell lung cancer treated with immunotherapy.

Reference

Anderson TM, Chang BH, Huang AC, et al. FDG PET/CT imaging 1 week after a single dose of pembrolizumab predicts treatment response in patients with advanced melanoma. Clin Cancer Res. Published online January 24, 2024. doi:10.1158/1078-0432.CCR-23-2390