MORE study data provide insight into predicting SIRT treatment outcomes

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Andrew S Kennedy

Investigators from the MORE (Metastatic colorectal cancer liver metastases outcomes after radioembolization) study have released new findings at the American Society of Clinical Oncology’s 2014 Gastrointestinal Cancers Symposium confirming that standard laboratory tests are a valuable tool for predicting patient outcomes prior to Selective Internal Radiation Therapy (SIRT). 

The MORE data demonstrates that diagnostic results showing organ function and biochemical blood levels offer insights into correctable levels to improve the patient’s response to SIRT. Andrew S Kennedy, director, Radiation Oncology Research, Sarah Cannon Research Institute, Nashville, USA, lead investigator of the MORE study, reported the findings.

Kennedy also presented a proposed method that enables complex modelling of the hepatic arterial route and the tumour microvascular bed in which the Y90-microsphere radioactive particles will become permanently embedded. This shows promise to more accurately outline the path microspheres take to the tumour arteriole end which may improve treatment success.

“Together, these findings provide valuable insights about the enhanced degree of precision that we can achieve as we seek to further improve patient outcomes using SIR-Spheres microspheres,” he said.

“The MORE study, which began in 2002, contains data from 606 metastatic colorectal cancer (mCRC) patients at 11 US institutions making it among the largest of all radioembolization studies,” reported Kennedy. “The study’s size and consistent results have allowed us to address one of the most common problems faced by the oncology community—once a mCRC patient has failed multiple lines of chemotherapy, there is no standard of care to battle the disease. These compelling results have increased understanding of SIRT as a treatment option for this unique patient population while highlighting the positive aspects of the safety and efficacy.”

Among the data collected in the retrospective review of MORE, were values for the following parameters 10 days prior to treatment: haemoglobin, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine. Common Terminology Criteria for Adverse Events (CTCAE) grades were assigned to each parameter and analysed for impact on survival by line of chemotherapy. Where applicable, consensus guidelines were used to establish the abnormal limits for SIRT.

The 606 patients were studied with a median follow-up of 8.5 months after SIRT. Fewer than 11% of patients were treated outside recommended guidelines, with grade 2 albumin being the most common at time of SIRT. Abnormal parameters were associated with statistically significantly decreased median survivals.

“The MORE team concluded that review of pre-SIRT laboratory parameters may aid in improving median survivals if abnormal values can be addressed prior to radiation delivery,” continued Kennedy. “These efforts are important in optimising treatment response to liver radiotherapy.”

Predictive modelling of the hepatic arterial tree and tumour microvasculature


Aimed at further advancing the SIRT treatment approach, fractal methods were used to develop a software tool representing the microvasculature of the human liver and different organs and can account for disease states such as liver tumours. Normal liver and tumour artery trees were created, with malignant vessels employing a random generator at each node resulting in corkscrew, bifurcation and/or trifurcation daughter vessel pattern. The team concluded that predictive modelling may now be possible for microspheres exiting from a catheter into the hepatic artery to its final position in a tumour end arteriole, or for systemic therapies.

 

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