Monitoring Therapy Response and Progression of Lung Cancer

You may be amidst cancer treatment, or your cancer may be in remission, but regardless of your current status, monitoring therapy response and progression of lung cancer remains an important part of your life. It allows for

• early detection of cancer progression
• customized adjustments to treatment
• extend survival and improve the chances of long-term remission for advanced patients

Overall, this is an aspect of cancer care that determines the best course of action for optimal care of patients. The assessments for response to therapies include

• Radiographic imaging of tumor size
• Monitoring changes in driver mutations
• Measurement of circulating tumor DNA
• Measurement of serum markers

Besides assessing the response to personalized treatments, these tests may be used to monitor cancer progression, or if the cancer has worsened.

Conventionally, the gold standard for monitoring therapy response and disease progression among lung cancer patients is computed tomography (CT) scans.

The current evaluation of tumor shrinkage is Response Evaluation Criteria In Solid Tumors (RECIST), a standard scoring method based on whether tumors

• Shrink
• Remain the same
• Increase in size

Although radiographic methodologies are useful, they may have limitations and errors. To overcome these challenges, researchers have developed new strategies, such as highly sensitive and specific ctDNA molecular tests and new radiographic imaging. Experts recommend using molecular tests alongside imaging techniques as a validation tool to improve the accuracy of therapeutic response assessment. This approach can provide patients with reassurance and optimism, knowing that alternative measures are available to address any limitations of specific tests.

Related: Radiographic Imaging in Monitoring Cancer Therapy Response

In the area of targeted therapies, advanced or metastatic non-small cell lung cancer (NSCLC) patients are now screened for the driver mutations causing their disease. For this purpose, the U.S. Food and Drug Administration (FDA) has approved a class of diagnostics for testing driver mutations called companion diagnostics. These tests help to match specific targeted agents to patients who are likely to benefit from it based on their molecular tumor profile.

Furthermore, these tests were also approved by the FDA to “monitor response to treatment with a particular therapeutic product for the purpose of adjusting treatment to achieve improved safety or effectiveness.”

Most of the FDA-approved companion diagnostics examine tissue specimens and thus, require patients to undergo routine invasive tissue biopsy after treatment. However, the latest development in companion diagnostics has placed three liquid biopsies on the FDA list of approval:

• FoundationOne Liquid CDx
• Guardant360 CDx
• Cobas EGFR Mutation Test v2

These minimally invasive assays have become of interest in the early detection of cancer progression and in monitoring therapy response. Some assays can even analyze or quantitate multiple driver mutations (such as EGFR, MET, ALK, KRAS and HER2) in a single assay, thanks to the high processing ability of next-generation sequencing (NGS).

The limitation of monitoring only the known driver mutations is that the malignant tumors are constantly evolving. Many can develop new, secondary mutations that resist the initial treatment. Your doctor may recommend an alternative assay for reasons like cost and accessibility.

Related: Types of Lung Cancer Biomarker Tests

These assays are a group of more personalized liquid biopsies that detect and profile any circulating tumor DNA (ctDNA) released into the bloodstream.

Minimal residual disease (MRD) is a new concept that compares the ctDNA signature before, during, and after cancer treatment with the primary tumor sample.

Using NGS, the assays inform changes in an individual’s ctDNA profile at any stage of the cancer journey to inform cancer recurrence. A positive MRD result may indicate little response to treatment or a rise in treatment resistance. Early detection of MRD may allow timely re-treatment or planning of second-line treatment.

Some MRD assays that are already in use:

• Signatera molecular disease residual assay
• Guardant Reveal
• Invitae Personalized Cancer Monitoring (PCM)

Related: Minimal Residual Disease Assays – Detecting Circulating Tumor DNA

Before the existence of gene tests, doctors examined fluctuations in protein markers in blood serum to detect cancer and monitor cancer progression. Serum markers associated with NSCLC:

• CA 15-3
• CA 125
• CYFRA 21-1
• SCC

Serum markers associated with SCLC:

• HE4 (human epididymis protein 4)
• NSE
• proGRP (progastrin-releasing peptide)

The major drawback of serum markers is that they are produced by both tumor and healthy cells. They may occur at a higher level under cancerous circumstances. But, non-cancerous health conditions, such as inflammation, can also trigger an increased production of these proteins.