Outcomes of Therasphere Radioembolization for Colorectal Metastases

doi:10.1016/j.clcc.2015.02.002

Clinical Colorectal Cancer

Volume 14, Issue 3, September 2015, Pages 146-153

https://doi.org/10.1016/j.clcc.2015.02.002 Get rights and content

Abstract

Introduction

The liver is the most common site for colorectal cancer (CRC) metastases. Radioembolization with yttrium-90 (Y90) represents an alternative approach in the management of unresectable hepatic colorectal metastases. The objective of this study was to evaluate outcomes after treatment with Y90.

Materials and Methods

A retrospective review of patients undergoing Y90 glass microsphere treatment for metastatic CRC from 2009 to 2013 was conducted. Multivariable analysis (MVA) of factors related to overall survival (OS) was performed using the Cox proportional hazard and OS estimates were calculated using the Kaplan–Meier method.

Results

We identified 68 patients. Median and 2-year OS were 11.6 months and 34%. For patients with ≤ 25% hepatic burden of disease (HBD) and 1 chemotherapy regimen, 2-year OS was 63%. Median and 2-year OS for patients with ≤ 25% versus > 25% HBD were 19.6 months and 42% versus 3.4 months and 0% (P < .0001). Univariate analysis revealed that higher HBD, ≥ 3 lines of chemotherapy received, and higher carcinoembryonic antigen (CEA) were found to be significant predictors of worse OS. MVA revealed age, > 25% HBD, ≥ 3 lines of chemotherapy, and higher CEA were independently prognostic for increased mortality, and resected status of the primary tumor was associated with decreased mortality. The presence of extrahepatic metastases was not prognostic. Toxicities were mild and only 5 patients experienced Grade 3/4 biochemical toxicity.

Conclusion

Introduction

Colon cancer remains the third most common cancer, and the third leading cause of cancer death, in the United States among men and women. In 2014, it was estimated that nearly 72,000 men and 65,000 women will be diagnosed with colorectal cancer (CRC) and 50,000 people will die of the disease.¹ Advances in systemic therapy have led to an improvement in relative 5-year survival rates of 65% for patients with colon cancer. Liver metastases are common, however, and up to 60% of patients will develop liver disease throughout the course of their disease. Synchronous liver metastases are present in 10% to 25% of patients at the time of diagnosis. Surgical resection of metastatic disease remains the standard of care with 5-year survival rates as high as 50% for the 20% to 25% of patients with resectable disease.2, 3, 4, 5, 6, 7, 8 Most patients, however, have unresectable disease, and their median survival is only 6 to 22 months.4, 8, 9, 10

Systemic therapy has long been considered the mainstay of therapy for treatment of unresectable metastatic disease with the goal of downstaging tumors for eventual resection. Many patients, however, will develop progressive disease that is unresponsive to chemotherapy. At this stage in the disease course local tumor treatment might be the best option for continued survival. Several treatment modalities have been developed to target unresectable liver metastases and include: radiofrequency ablation (RFA), transarterial chemoembolization (TACE), radioembolization (RE) with yttrium-90 microspheres (Y90), hepatic arterial infusion chemotherapy with floxuridine, and standard conformal external beam or stereotactic body radiation therapy.

Radioembolization targets hepatic neoplasms by using the dual blood supply of the liver to deposit radioactive microspheres in the periphery of the tumor via percutaneous catheterization of the hepatic artery. This allows high irradiation doses to be delivered directly to the tumor and spares the normal liver parenchyma. Y90 RE can be performed using glass or resin microspheres. The resin microspheres (SIR-Spheres, SIRTex Medical, Ltd, Sydney, Australia) have been more commonly used in the treatment of CRC liver metastases in the United States, and glass microspheres (TheraSphere; BTG International, London, England) have been extensively studied in the treatment of hepatocellular cancer. The advantage of the glass microspheres, however, is that they are smaller and less embolic, 20 to 30 μm versus 20 to 60 μm, and have a greater per particle radioactivity compared with the resin microspheres.4, 11, 12, 13 Y90 has been proven to be a safe method of radiation delivery with minimal systemic toxicity.14, 15, 16, 17 The objective of this study was to evaluate outcomes including overall survival (OS) and toxicity after treatment with Y90 in patients with unresectable hepatic metastases from CRC.

Section snippets

Materials and Methods

A retrospective review of patients who presented with unresectable CRC liver-dominant metastases who underwent treatment with Y90 from 2009 to 2013 was conducted after obtaining appropriate institutional review board approval. Patient demographic, tumor, and treatment characteristics were evaluated.

Results

There were 68 patients included for review in this study. The median age of the cohort was 62 years. Most patients were male (n = 38, 55.9%) had an ECOG performance status of 0 or 1 (n = 46, 97.1%), had primary colon cancer (n = 56, 82.4%), and had resection of their primary tumor (n = 57, 85%). Only 23 (33.8%) patients had previous intervention for their hepatic disease (surgical resection, RFA, or TACE) before receiving Y90 and all but 1 patient received chemotherapy before Y90 treatment. The

Discussion

In this cohort of patients with unresectable liver metastases from CRC, we were able to demonstrate that Y90 with glass microspheres provides an acceptable median OS with minimal toxicity. Our data suggest that patients who have a lower HBD and minimal exposure to chemotherapy have the greatest potential benefit from therapy because they demonstrated an improved OS compared with patients who did not receive treatment with Y90 until they had extensive disease or had undergone multiple rounds of

Conclusion

Yttrium-90 was associated with acceptable OS with minimal morbidity in this series. Minimal exposure to chemotherapy and low HBD were found to be associated with better OS, however, even patients with chemotherapy-refractory disease received a benefit from treatment. These results highlight the need for additional prospective studies that evaluate Y90 as part of the early treatment regimen in unresectable disease and the advantages in treating patients with refractory disease.

Disclosure

The authors have stated that they have no conflicts of interest.

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View full text

Original StudyOutcomes of Therasphere Radioembolization for Colorectal Metastases

Abstract

Introduction

Materials and Methods

Results

Conclusion

Introduction

Section snippets

Materials and Methods

Results

Discussion

Conclusion

Disclosure

J Am Coll Surg

Int J Radiat Oncol Biol Phys

J Vasc Interv Radiol

Int J Radiat Oncol Biol Phys

J Vasc Interv Radiol

Ann Oncol

Colorectal cancer statistics, 2014

CA Cancer J Clin

Short-term outcomes after combined colon and liver resection for synchronous colon cancer liver metastases: a population study

Ann Surg Oncol

Local therapies for hepatic metastases

J Natl Compr Canc Netw

Intra-arterial therapies for metastatic colorectal cancer

Semin Intervent Radiol

Combined colon and hepatic resection for synchronous colorectal liver metastases

J Surg Oncol

Survival after hepatic resection of colorectal cancer metastases: a national experience

Cancer

Surgical therapy for metastatic disease to the liver

Annu Rev Med

A systematic review on the safety and efficacy of yttrium-90 radioembolization for unresectable, chemorefractory colorectal cancer liver metastases

J Cancer Res Clin Oncol

Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres

Cancer

Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis

Eur Radiol

Original Study
Outcomes of Therasphere Radioembolization for Colorectal Metastases