patient care perspectives

Imaging in the Era of Precision Therapy for Non–Small Cell Lung Cancer

by Bruce E. Johnson, MD

Overview

Imaging is valuable in assessing the disease at presentation and guiding targeted therapy with tyrosine kinase inhibitors (TKIs). Continued TKI therapy beyond Response Evaluation Criteria in Solid Tumors (RECIST) progression is a paradigm that requires individualization. For some patients with non–small cell lung cancer (NSCLC), the duration of TKI treatment can be extended in an effort to maximize the yield from each therapy.

Expert Commentary

Bruce E. Johnson, MD

Institute Physician
Dana-Farber Cancer Institute
Professor of Medicine
Harvard Medical School
Boston, MA

“When your patient experiences this rather dramatic decline in tumor volume with the targeted therapy, it is particularly important that you do not stop the TKI too soon.”

Bruce E. Johnson, MD

In the initial diagnostic effort to assess the state of patients’ disease, our standard in the era of precision medicine is a computed tomography scan of the chest that goes to the abdomen and adrenal gland, a positron emission tomography/computed tomography scan to look for evidence of distant metastasis, and, lastly, a brain magnetic resonance imaging scan, given that 10% to 20% of patients presenting with NSCLC have brain metastasis. 

As for imaging to assess responses in patients on precision therapies, the most data are available for EGFR-mutant disease, which is seen in 10% to 15% of patients with advanced NSCLC; ALK rearrangements are present in approximately 3% to 5% of patients. The vast majority of patients with these targets will respond to the appropriate TKIs. We typically reimage patients with EGFR mutations after 8 weeks of therapy, and for those who respond, we see an average reduction in tumor volume of approximately 60% (although it can be as low as 0% and as high as 99%). The tumor typically stays at that level for 2 to 6 months and then, depending on the TKI and/or the rearrangement, we begin to see slow growth between 6 and 18 months after the initiation of therapy. When your patient experiences this rather dramatic decline in tumor volume with the targeted therapy, it is particularly important that you do not stop the TKI too soon because, even though the tumor starts to grow, the growth will often be slow and thus you can extend the duration for which the TKI works. Among patients with EGFR mutations who develop slow growth, on average, it is approximately 5 months from the time you see RECIST progression until the person develops either symptomatic progression or a new metastasis. Perhaps most importantly, one-quarter of patients can be treated for 1 year after they develop RECIST progression. 

The behavior of tumors with ALK rearrangements is similar, with an average decline in tumor size at 8 weeks of approximately 60% among responders, and slow growth beginning between 6 and 18 months. For those who develop relatively rapid symptomatic progression, we do not advocate for continuing with the TKI, but, for those with slow growth and a reduced tumor size, we try to get as much as possible out of each treatment. Overall survival for ALK-positive patients who started on crizotinib up front may now be longer than 4 to 5 years.

It is also important to monitor the central nervous system (CNS) because, although TKIs penetrate the CNS, you can see progression in the CNS even when the disease is controlled systemically. For those who develop a single brain metastasis or a limited number of brain metastases, you can surgically resect them or irradiate them locally and continue on with the systemic treatment if it remains in control.

References

Digumarthy SR, Mendoza DP, Lin JJ, et al. Computed tomography imaging features and distribution of metastases in ROS1-rearranged non-small-cell lung cancer. Clin Lung Cancer. 2020;21(2):153-159.e3.

Gambazzi F, Frey LD, Bruehlmeier M, et al. Comparing two imaging methods for follow-up of lung cancer treatment: a randomized pilot study. Ann Thorac Surg. 2019;107(2):430-435.

Hida T, Dahlberg SE, Lydon CA, et al. Tumor volume analysis as a predictive marker for prolonged survival in anaplastic lymphoma kinase-rearranged advanced non-small cell lung cancer patients treated with crizotinib. J Thorac Imaging. 2020;35(2):101-107.

Lo PC, Dahlberg SE, Nishino M, et al. Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer. Cancer. 2015;121(15):2570‐2577.

Mattonen SA, Davidzon GA, Benson J, et al. Bone marrow and tumor radiomics at 18F-FDG PET/CT: impact on outcome prediction in non–small cell lung cancer. Radiology. 2019;293(2):451-459.

Mendoza DP, Lin JJ, Rooney MM, et al. Imaging features and metastatic patterns of advanced ALK-rearranged non-small cell lung cancer. AJR Am J Roentgenol. 2020;214(4):766-774.

Nakagawa K, Hida T, Nokihara H, et al. Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2020;139:195‐199.

Peters S, Mok TSK, Gadgeel SM, et al. Updated overall survival (OS) and safety data from the randomized, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC. J Clin Oncol. 2020;38(suppl):9518.

Watanabe S, Hayashi H, Okamoto K, et al. Progression-free and overall survival of patients with ALK rearrangement-positive non-small cell lung cancer treated sequentially with crizotinib and alectinib. Clin Lung Cancer. 2016;17(6):528‐534.

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