TheraSphere® For Treatment of Metastases in Liver
Condition: Colorectal Cancer Metastatic; Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional

Summary: 
      To investigate whether the dose predicted by pre-therapy 99mTc MAA SPECT predicts the dose to
      the liver from the 90Y microspheres as assessed by post-therapy 90Y SPECT/CT or positron
      emission tomography (PET)/CT.
    

Detailed description: 
      This study will acquire imaging information from 3-5 patients that will demonstrate
      feasibility of future implementation of personal dosimetry-based treatment planning for
      Trans-arterial Radio-embolization (TARE).

      TARE therapy of liver neoplasia using 90Y-theraspheres has a long history. The device is FDA
      approved for the treatment of hepatocellular carcinoma, but has been used extensively for
      treatment of secondary liver neoplasia, including metastatic colorectal lesions under
      Humanitarian Device Exemption protocols such as this one.

      As a targeted radioactive therapy, the current TARE implementation suffers from a lack of
      efficiency characteristic of radiopharmaceutical therapy (RPT) in general; namely, that the
      activity determined to treat the patient is not optimized according to normal organ tolerated
      absorbed dose and tumor efficacy thresholds. The amount of activity to be administered is
      determined from volumetrics established from associated imaging, either MRI or X-ray CT,
      where the total volume of irradiated tissue is considered as irrigated by the artery selected
      for administration, including both tumor and normal organ tissue. From this volume
      determination, the activity necessary to deliver an average pre-determined safe absorbed dose
      (120 Gy) to the entire irradiated region is calculated and administered.

      In RPT, in the theranostic paradigm, a pre-therapeutic, or surrogate, quantity of activity is
      administered to the patient; 3D imaging (SPECT/CT or PET/CT) is then acquired at several time
      points and the individual patient's pharmacokinetics are determined, the normal organ and
      tumor dosimetry are performed and the optimal administered activity calculated that will
      deliver safe and efficacious treatment for the individual patient is determined, generally
      limited by the normal organ at risk maximum tolerated dose.

      TARE presents a number of unique characteristics that enable a simpler version of this
      approach than is typical for most RPT. The method of administration means that only the
      normal liver and lungs need to be considered as potential organs at risk as the microspheres
      embolize and do not circulate systemically; the lack of associated photons in the 90Y decay
      chain means that a simple activity-to-dose-rate conversion can be used; the embolization
      means that only a single imaging time point is necessary as there is no redistribution of
      activity over time and the dose rate is converted to absorbed dose using the physical decay
      parameters of 90Y. These natural simplifications are already exploited in the current
      volumetric paradigm, where a 99mTc-macro albumin aggregate (MAA) surrogate and planar imaging
      are used to determine the fraction of total activity that is shunted to the lung and where a
      derived conversion factor is used to convert activity to absorbed dose.

      The technical complication in TARE is that the surrogate (99mTc-MAA) has a different nature
      from the therapeutic device (90Y-theraspheres), and thus the reliability of the predictive
      quality of the surrogate is disputed. However, with precise and advanced imaging
      reconstruction and dosimetry the investigators have shown the ability to accurately and
      precisely predict normal liver and tumor average 90Y-therasphere uptake and absorbed dose
      from 99mTc-MAA.

      This protocol seeks to acquire the imaging information from 3-5 patients that will
      demonstrate feasibility of future implementation of personal dosimetry-based treatment
      planning for TARE. In addition to the clinical standard of care assessments: 1. a single
      SPECT/CT instead of the current planar image will be acquired of the surrogate 99mTc-MAA; 2.
      An additional single 3D image (either SPECT/CT or PET/CT, depending on machine availability)
      will be acquired up to 6 hours post-administration of the therapeutic 90Y-microspheres for
      comparison. Informed consent will be obtained.
    

Intervention name(s): Therasphere Therapy
Intervention type(s): Other
Intervention description(s): TheraSphere is a radiotherapy treatment for primary and secondary liver neoplasia. This is an imaging study that will examine 3-5 patients who have been treated for metastatic colorectal cancer in the liver using TheraSphere®. Participation in the study involves an additional post-treatment SPECT/CT or PET/CT scan at (0-6) hours.
Intervention model: Single Group Assignment
Intervention model description: To investigate whether the dose predicted by pre-therapy 99mTc MAA SPECT predicts the dose to the liver from the 90Y microspheres as assessed by post-therapy 90Y SPECT/CT or PET/CT.
Masking: None (Open Label)
Primary purpose: Other