Y90 for lung cancer mets to liver?

Y90 Transarterial Radioembolization of Primary Lung Cancer Metastases to the Liver

Clinical question

Is Yttrium-90 transarterial radioembolization safe and effective in patients with primary lung cancer metastasized to the liver?

Take away point

This retrospective analysis of 57 patients with lung cancer metastatic to the liver demonstrated effectiveness on local control and progression free survival. Overall, the treatment suggested an acceptable safety profile, with 11 severe or life-threatening adverse events within 30 days.

Reference

Yttrium-90 Transarterial Radioembolization of Primary Lung Cancer Metastases to the Liver. Alexander, E M.D. et al Journal of Vascular and Interventional Radiology, Volume 35, Issue 2, 214-225.

Click here for abstract

Study design

The study was a retrospective, observational, descriptive, single center study.

Funding Source

NIH/NCI Cancer Center Support Grant P30

Setting

Memorial Sloan Kettering Cancer Center, New York

Figure

Figure 1. A 55-year-old woman with EGFR-mutant NSCLC with progressing liver metastases in the left hepatic lobe. (a) Axial portal venous-phase CT image demonstrated a lesion in segment IV (arrow), resulting in biliary dilatation. (b) Coronal portal venous-phase CT image demonstrated the lesion (arrow). (c) Angiography of the celiac axis demonstrated the left hepatic artery (arrow) and the middle hepatic artery (arrowhead), where resin microspheres were delivered in a split administration. (d) Axial portal venous-phase CT image obtained 6 months after yttrium-90 radioembolization showed atrophy of the treated left hepatic lobe with persistence of biliary dilatation (arrow). (e) Coronal portal venous-phase CT image demonstrated marked size reduction of the tumor (arrow). CT = computed tomography; EGFR = epidermal growth factor receptor; NSCLC = non–small cell lung cancer.



Figure 4. Overall survival in months was estimated using the Kaplan–Meier (KM) method. NSCLC = non–small cell lung cancer; SCLC = small cell lung cancer.

Summary

Lung cancer is the second most diagnosed cancer in the United States with approximately 40% of patients presenting at diagnosis with metastatic disease. Patients with metastatic disease to the liver indicates a worse prognosis compared to metastasis at other sites, with an overall survival of 3 months for patients with non-small cell lung cancer or small cell lung cancer. Treatment options are limited to systemic therapies such as chemotherapy, targeted therapy, and immunotherapy. Several small case series have demonstrated the use of radioembolization with an acceptable safety profile that prompted further investigation.

The authors of this paper assessed the safety and effectiveness of yttrium-90 transarterial radioembolization in patients with primary lung cancer metastasized to the liver. They performed a retrospective study of 57 patients who were treated between August 2010 and May 2021. Treatments were delivered with either glass or resin microspheres. Primary outcomes of this study were safety, local progression-free survival, and overall survival after yttrium-90 treatment. Clinical laboratory values, biochemical toxicities and radiographic response were monitored approximately 1 month after treatment and at 3-month intervals thereafter.

Of the 79 treatments reviewed, 40 (51%) were associated with side effects within 1 month of yttrium-90 treatment. 29 of those patients experienced mild-moderate adverse events, which included self-limited post-embolic syndrome with symptoms of fatigue, abdominal pain, nausea, and weakness. There were 9 serious adverse events that required prolonged hospitalization or unplanned escalation of care. There was 1 life threatening event marked by acute renal failure and 1 death of a patient from pneumonia. Of note, there were statistically significant increases in aspartame transaminase and alkaline phosphatase at 1 month post treatment. At 3 months, these levels remained high with the addition of increases in total bilirubin, and alanine transaminase. 17 of the patients developed ascites with a median occurrence 19.2 months after treatment.

RECIST 1.1 was used to evaluate treatment response within 6 months of radioembolization, with median local progression free survival of 7.6 months for non-small cell lung cancer, 3.6 months for small cell lung cancer, and 30.6 months for lung carcinoids. Median overall survival was 8.3 months for non-small cell lung cancer, 4.1 months for small cell lung cancer, and 43.5 months for lung carcinoids. For non-small cell lung cancer, presence of bilobar disease, more tumors, and lobar treatment were negative predictors of overall survival. For lung carcinoids, tumor involvement of >50% was a negative predictor of overall survival.

Limitations of this study include the retrospective study design from a single institution and the small patient cohort. The difference in prognoses between the primary lung cancers and the differences in microsphere, volume, and formulation of the therapeutic treatment presented additional limitations.

Commentary

This study demonstrated that yttrium-90 transarterial radioembolization can treat primary lung cancers metastasized to the liver with an acceptable safety profile. The greatest effectiveness of the treatment was observed with lung carcinoid tumors, which had significantly longer baseline local progression-free survival and overall survival when compared to small cell and non-small cell lung cancer.

Historically, transarterial radioembolization was often used after failure of multiple lines of therapy. Liver decompensation and ascites due to overall disease progression and hepatotoxic medications are difficult to distinguish from adverse effects attributable to the yttrium-90 treatment. Since treating refractory tumors with larger tumor burden have known increased risks of late occurring adverse events, studies like this are important to assess yttrium-90 transarterial radioembolization’s safety profile and delineate its role in the treatment algorithm of lung cancer liver metastases.

In this author’s opinion, the next steps for this promising treatment option in patients with lung cancer metastases to the liver involve prospective studies targeting a single type of lung cancer with a uniform therapeutic delivery method. Prognostication models for late occurring adverse events should be investigated to better triage patients for yttrium-90 transarterial radioembolization and allow close-interval follow-ups. Lastly, combination therapies of yttrium-90 transarterial radioembolization and systemic therapies demand further investigation.

Post Author

Anthony M. Camargo, BA
MD candidate, Class of 2025
University of Massachusetts Chan Medical School
@anthonymcamargo