Decoding Brain Metastases: The Power of 18F-Fluciclovine PET

Brain metastases, or secondary brain tumors, occur when cancer cells spread from their original site to the brain.

This devastating complication affects around 10-30% of adults with cancer, making it a significant concern in cancer management.

One of the greatest challenges in dealing with brain metastases is distinguishing between radiation necrosis and tumor progression post-radiation therapy, a scenario that has been a conundrum for physicians worldwide.

Traditional diagnostic methods, including MRI, have limitations when it comes to identifying recurrent brain metastases.

The breakthrough we’ve been hoping for may be on the horizon.

Thanks to a recent study known as PURSUE. This exciting research explores using 18F-Fluciclovine Positron Emission Tomography (PET), a novel imaging technique, in detecting recurrent brain metastases.

In this article, we’ll go into the details of the study, its implications, and the promising future it heralds for brain metastases detection.

The Need for Improved Diagnostic Methods

In the ongoing fight against cancer, effective and precise diagnostic tools are paramount.

This is particularly true in the realm of brain metastases.

Once a cancer patient undergoes radiation therapy, one of the most formidable challenges is differentiating between radiation necrosis and tumor progression.

Radiation necrosis, a noncancerous condition, can mimic the growth of a cancerous tumor, making accurate diagnosis a complex task.

Traditional diagnostic methods, such as Magnetic Resonance Imaging (MRI), have been used for years to detect recurrent brain metastases.

While MRI provides detailed images of the brain, its ability to differentiate between radiation necrosis and tumor progression has been a subject of debate.

This is due to similarities in the appearance of radiation necrosis and recurrent tumors on the MRI scan.

Such limitations of MRI can result in false-positive or false-negative results leading to unnecessary treatments or missed therapeutic opportunities.

Therefore, there’s an urgent need for more precise diagnostic tools that can accurately detect the presence of recurrent brain metastases and distinguish them from radiation necrosis.

The recent PURSUE study addresses this need by exploring the potential of 18F-Fluciclovine PET, a novel imaging technique, in detecting recurrent brain metastases.

18F-Fluciclovine PET: A Promising Solution

In the quest to improve the detection and management of recurrent brain metastases, 18F-Fluciclovine Positron Emission Tomography (PET) emerges as a beacon of hope.

This novel imaging technique, now under detailed investigation, could revolutionize the way we diagnose recurrent tumors in the brain.

18F-Fluciclovine, also known as Axumin, is a radiotracer designed to help visualize the presence and location of specific types of cancer.

When used in a PET scan, this radiotracer can effectively detect cancerous cells that have a high rate of amino acid transport, a characteristic often seen in brain metastases.

Enter the PURSUE study.

This is an open-label, single-arm, single-dose, multicenter phase 2b study designed to establish image interpretation criteria for 18F-Fluciclovine PET in detecting recurrent brain metastases after radiation therapy.

This cutting-edge study explores the potential of 18F-Fluciclovine PET to differentiate between radiation necrosis and recurrent brain metastases, which could offer a solution to one of the biggest challenges in the management of brain metastases.

Exploring the PURSUE Study: A Step Towards Improved Diagnostic Performance

The PURSUE study (NCT04410367) represents a groundbreaking leap in our understanding and diagnosis of recurrent brain metastases.

The methodology and design of this study provide valuable insights into the capabilities of 18F-Fluciclovine PET and its potential role in future diagnostics.

The study enrolled patients with solid tumor brain metastases across seven US sites.

Inclusion criteria involved patients with a ‘reference’ lesion, previously irradiated, and equivocal on MRI for recurrence, and planned for craniotomy.

The administration of the 18F-Fluciclovine PET took place within 42 days post-MRI and between 1-21 days pre-craniotomy.

Three independent blinded readers assessed the uptake of the lesion 18F-Fluciclovine qualitatively.

The uptake was visually rated as:

• “mild” (up to blood pool)

• “moderate” (above blood pool to parotid)

• or, “marked” (above parotid).

Additionally, the study also focused on several quantitative metrics for assessing the uptake of the 18F-Fluciclovine.

The primary endpoint of the PURSUE study was the diagnostic performance (sensitivity, specificity, positive-, and negative-predictive value [PPV/NPV]) of different thresholds of lesion 18F-Fluciclovine uptake on qualitative, visual reads vs central histopathological analysis.

In simpler terms, it aimed to find out how well the PET scan results correlated with actual tissue analysis, thus determining its accuracy in detecting recurrent brain metastases.

The Results of the PURSUE Study: A Breakthrough in Detecting Recurrent Brain Metastases

The results of the PURSUE study unveiled valuable insights into the performance of 18F-Fluciclovine PET in detecting recurrent brain metastases.

The study evaluated 23 reference lesions in 23 subjects, of which 10 (43%) were confirmed as recurrent tumors through histopathological analysis.

One of the most promising findings was the high sensitivity of the ‘marked’ qualitative measure. This rating indicated a sensitivity range of 92-100%, although the specificity varied between 40-80% across different readers. The high sensitivity means that 18F-Fluciclovine PET was highly accurate in detecting true positive cases of recurrent brain metastases.

Another significant finding was the performance of SUVmax, a reader-independent, quantitative metric.

The SUVmax threshold of 4.8 demonstrated a sensitivity of 80% and a specificity of 85%. The high specificity indicates a low chance of false positives, meaning that when the PET scan indicates a recurrence, it is highly likely to be accurate.

Based on these metrics, the study established image interpretation criteria: lesions with 18F-Fluciclovine uptake of an SUVmax equal to or greater than 4.8, or visually greater than the parotid gland, should be considered suspicious for recurrence.

Otherwise, a recurrence should be considered unlikely.

Application of these criteria resulted in a sensitivity of 80%, specificity of 77-85%, PPV of 73-80%, and NPV of 83-85% across the readers. These results show that 18F-Fluciclovine PET, with its high performing diagnostic capabilities, can be a game-changing tool in detecting recurrent brain metastases.

Dr. Rupesh Kotecha on the Future of Brain Metastases Detection

According to renowned radiation oncologist Dr. Rupesh Kotecha, there’s an emerging beacon of hope for patients battling brain metastases and their medical teams.

His recent study focusing on using 18F-Fluciclovine PET imaging for detecting recurrent brain metastases after radiation therapy could revolutionize the field of neuro-oncology.

Dr. Kotecha explained the magnitude of the issue, stating that “patients with brain metastasis who are treated with radiosurgery are often told at least 50% of the time, at least, that at least one of their previously treated lesions has increased in size at some point.”

This increase in lesion size, as detected by an MRI, is a point of concern and a cause for considerable anxiety for both the patient and the medical team.

This issue arises because an increase in lesion size could either mean recurrent or progressive disease, or treatment-related changes.

The potential misinterpretation of these changes could result in either unnecessary surgery or a continuation of an ineffective therapy.

Dr. Kotecha highlights the critical need for a more reliable diagnostic tool saying “this is critical for clinical care”.

The prospective phase 2 multicenter trial that he mentioned sought to evaluate an alternative approach to conventional MRI. The study used an amino acid PET CT scan, specifically with 18F-Fluciclovine, to differentiate between the two processes, i.e., recurrence and treatment-related changes.

The study included patients who had previously irradiated solid tumor brain metastasis that had an increase in lesion size, making them equivocal on MRI for recurrent disease.

Dr. Kotecha further elaborated that “when we looked at the final histopathology, 43% were confirmed as recurrent tumor, and 57% were negative per recurrent tumor”.

These promising results highlight the potential of 18F-Fluciclovine PET as an effective diagnostic tool.

“The highest performing qualitative measure was considered marked activity…resulting in a sensitivity of 40 to 80% specificity of 92 to a hundred percent a positive predictive value of 89 to a hundred percent, and a negative predictive value of 68 to 86%”, asserted Dr Kotecha.

The study has set forth a method for visual interpretation of the amino acid PETs and continues to refine standalone qualitative criteria for better results in future studies. One such study is the phase 3 REVELATE study, which has completed its accrual and awaits analysis.

Dr. Kotecha, affiliated with Baptist Health Baptist Hospital and a respected figure in the field with his medical degree from Michigan State University College of Human Medicine, holds this study in high regard. He describes it as unique and the first of its kind to evaluate PET characteristics of suspected recurrent brain metastases after radiation therapy.

He further added that “this study potentially provides access to a new imaging agent that can be game changing for our patient population.”

Recently, we had the chance to interview Dr. Kotecha during the ASCO 2023, you can learn more about this subject in the next video:

Conclusion: The Road Ahead in Detecting Brain Metastases

The journey in uncovering and treating brain metastases has been long and challenging.

The difficulty in distinguishing between radiation necrosis and tumor progression has often left physicians and patients alike in a state of uncertainty.

Yet, the advancements we’ve discussed here today are setting the stage for an optimistic future in this field.

The introduction of 18F-Fluciclovine PET has marked a significant turning point in our ability to detect recurrent brain metastases.

The results of the PURSUE study highlight the efficacy of this diagnostic tool, offering a ray of hope to those battling this challenging condition.

Key takeaways from the PURSUE study include:

• The high sensitivity and specificity of 18F-Fluciclovine PET in detecting recurrent brain metastases.

• The establishment of image interpretation criteria, which will guide the use of this diagnostic tool in clinical settings.

• The potential for 18F-Fluciclovine PET to improve patient outcomes by enabling more accurate and tailored treatments.

Lastly, insights from renowned experts like Dr. Rupesh Kotecha emphasize the immense potential that these advancements hold for the future.

The path to better diagnostics and treatments is a continuing journey.

But as we learn more, innovate, and refine our tools and techniques, the future of detecting and treating brain metastases looks promising.