BlueCross and BlueShield of Montana Medical Policy/Codes
Direct Brain Infusion of Therapeutic Agents
Chapter: Surgery: Procedures
Current Effective Date: July 18, 2013
Original Effective Date: July 18, 2013
Publish Date: July 18, 2013
Description

Treatment of central nervous system (CNS) diseases can be difficult because the blood brain barrier (BBB) limits or blocks delivery of drug molecules to the brain.  Direct interstitial infusion is a technique that aims to deliver therapeutic agents to targeted brain tissue in both small and large areas, thus bypassing the BBB.  One technique for infusion is convection-enhanced delivery (CED); with this technique drugs can be directly delivered to the tumor or area of the brain region via pressure infusion.  The technique has been proposed for treatment of brain tumors, Parkinson disease, epilepsy and other brain disorders.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Investigational

Blue Cross and Blue Shield of Montana (BCBSMT) considers interstitial infusion of therapeutic agents directly into the brain through an infusion catheter experimental, investigational and unproven.

Rationale

No randomized controlled trials have established superiority of blood brain barrier disruption (BBBD) techniques over the use of chemotherapy.  Although these techniques have been used for over twenty years, their efficacy has not been established.  Chemotherapy with BBBD has been associated with a higher risk of complications that include seizures, focal neurologic deficits, obtundation, cerebral herniation, stroke and death.  These complications are then multiplied by the side-effects related to the chemotherapy itself.  The Centers for Medicare and Medicaid (CMS) issued a National Coverage Determination that states that the use of osmotic BBBD is not reasonable and necessary when it is used as a part of a treatment regimen for brain tumors.

A search of the literature was completed through MEDLINE database through November 2008.  There is limited scientific data to permit conclusions regarding the use of direct brain infusion catheter(s) in the brain for delivery of therapeutic agent(s), and for the treatment of brain tumors, Parkinson disease, epilepsy or other disorders of the brain.  Although the ongoing clinical trial data is promising, further study is needed to demonstrate whether the use of this therapy leads to improved outcomes.

2011 Update

A search of peer reviewed literature was performed through November 2011.  The following is a summary of the key literature to date.

Bruce, J.N., et al. carried out a prospective, dose-escalation phase 1b study to assess the safety profile of convection-enhanced delivery of the chemotherapeutic agent, topotecan, for the management of  recurrent malignant gliomas, as well as evaluate radiographic response and survival.  The reported results indicated “Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated.”  The study established the maximum tolerated dose for future phase II studies.  “The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials” was noted by the authors.

Although the study is promising, further studies are needed.  This update failed to identify any additional information that would change the coverage position of this medical policy.

Coding

Disclaimer for coding information on Medical Policies        

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers.  Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

Experimental, investigational and unproven for all diagnoses.

ICD-10 Codes

Experimental, investigational and unproven for all diagnoses.

Procedural Codes: 0169T
References
  1. Broaddus, W.C., Prabhy, S.S., et al.  Distribution and stability of antisense phosphorothioate oligonucleotides in rodent brain following direct intraparenchymal controlled-rate infusion.  Journal of Neurosurgery (1998 April) 88(4):734-42.
  2. Prabhu, S.S., Broaddus, W.C., et al.  Distribution of macromolecular dyes in brain using positive pressure infusion:  a model for direct controlled delivery of therapeutic agents.  Surgical Neurological (1998 October) 50(4): 367-75; discussion 375.
  3. Morrison, P.F., Chen, M.Y., et al.  Focal delivery during direct infusion to brain:  role of flow rate, catheter diameter, and tissue mechanics.  American Journal of Physiology (1999 October) 277(4 Pt 2):R1218-29.
  4. Haar, P.J., Stewart, J.E., et al.  Quantitative three-dimensional analysis and diffusion modeling of oligonucleotide concentrations after direct intra parenchymal brain infusion.  IEEE Transactions on Biomedical Engineering (2001 May) 48(5):560-9.
  5. Gill, S.S., Patel, N.K., et al.  Direct Brain infusion of glial cell-line derived neurotrophic factor in Parkinson disease.  Nature Medicine (2003 May) 9(5):589-95.
  6. Gillies, G.T., Smith, J.H., et al.  Positive pressure infusion of therapeutic agents into brain tissues:  mathematical and experimental simulations.  Technology and Health Care (2005) 13(4):235-43.
  7. Gill, S.S., Patel, N.K., et al.  Addendum: Direct Brain infusion of glial cell-line derived neurotrophic factor in Parkinson disease.  Nature Medicine (2006 April) 12(4):479.
  8. Kim, J.J., Mareci, T.H., et al.  Voxelized model of interstitial transport in nervous tissue following direct infusion into white matter.  IEEE English Biological Society (2007):2114-7.
  9. Weingart, J., Grossman, S.A., et al.  Phase I trial of polifeprosan 20 with carmustine implant plus continuous infusion of intravenous 06-benzylguanine in adults with recurrent malignant glioma:  new approaches to brain tumor therapy CNS consortium trial.  Journal of Clinical Oncology (2007 February 1) 25(4):399-404.
  10. Centers for Medicare and Medicaid Services (CMS).  Decision Memo for Blood Brain Barrier Disruption (BBBD) Chemotherapy (CAG-00333N).  Medicare Coverage Database. Baltimore, MD: CMS; (2007 March 20). Available at: https://www.cms.hhs.gov .
  11. Sampson, J.H., Raghavan, R., et al.  Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin.  AJR American Journal of Roentgenology (2007 March) 188(3):703-9.
  12. Rogawski, M.A.  Convection-Enhanced Delivery in the Treatment of Epilepsy.  Neurotherapeutics (2009 April) 6(2):344-351.
  13. Bruce, J.N., Fine, R.L.  Regression of recurrent malignant gliomas with convection-enhanced delivery topotecan.  Neurosurgery (2011 December) 69(6):1272-80.
History
May 2013  New 2013 BCBSMT medical policy.  Interstitial infusion of therapeutic agents directly into the brain through an infusion catheter is considered experimental, investigational and unproven. 
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Direct Brain Infusion of Therapeutic Agents