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Date Printed: June 23, 2017: 11:44 AM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

05-86000-11

Original Effective Date: 12/15/02

Reviewed: 10/19/16

Revised: 11/15/16

Subject: Chemoresistance and Chemosensitivity Assays

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines
           
Other References Updates    
           

DESCRIPTION:

In vitro chemoresistance and chemosensitivity assays have been developed to provide information about the characteristics of an individual patient’s malignancy to predict potential responsiveness of their cancer to specific drugs. These assays are sometimes used by oncologists to select treatment regimens for an individual patient. Several assays have been developed that differ with respect to processing of biologic samples and detection methods. However, all involve similar principles and share protocol components including: (1) isolation of cells and establishment in an in vitro medium (sometimes in soft agar); (2) incubation of the cells with various drugs; (3) assessment of cell survival; and (4) interpretation of the result.

A variety of chemosensitivity and chemoresistance assays have been clinically evaluated in human trials. All assays use characteristics of cell physiology to distinguish between viable and nonviable cells to quantify cell kill following exposure to a drug of interest. With few exceptions, drug doses used in the assays are highly variable depending on tumor type and drug class, but all assays require drug exposures ranging from several-fold below physiologic relevance to several-fold above physiologic relevance. Although a variety of assays examine chemosensitivity or chemoresistance, only a few are commercially available.

POSITION STATEMENT:

In vitro chemosensitivity assays (e.g. ChemoFx, CorrectChemo) are considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

In vitro chemoresistance assays, including, but not limited to, extreme drug resistance assays, are considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

BILLING/CODING INFORMATION:

CPT Coding:

81535

Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by DAPI stain and morphology, predictive algorithm reported as a drug response score; first single drug or drug combination (investigational)

81536

Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by DAPI stain and morphology, predictive algorithm reported as a drug response score; first single drug or drug combination, each additional single drug or drug combination (List separately in addition to code for primary procedure) (investigational)

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage products:

The following National Coverage Determination (NCD) was reviewed on the last guideline reviewed date: Human Tumor Stem Cell Drug Sensitivity Assays (190.7) located at cms.gov.

The following Local Coverage Determination (LCD) was reviewed on the last guideline reviewed date: Noncovered Services (L33777) located at fcso.com.

DEFINITIONS:

No guideline specific definitions apply.

RELATED GUIDELINES:

None applicable.

OTHER:

Note: The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Examples of in vitro chemosensitivity and in vitro chemoresistance assays:

Adenosine Triphosphate (ATP) Chemotherapy Response
Afluorescent Cytoprint
ChemoFx
CorrectChemo (formerly Microculture Kinetic (MICK)
Differential Staining Cytotoxicity (DISC)
EVA/PCD
Extreme Drug Resistance (EDR)
Flow Cytometric Chemosensitivity
Fluorescence (cytoprint)
Fluorometric Microculture Cytotoxicity
Histoculture Drug Response
Human Tumor Cloning (HTCA)
Human Tumor Stem Cell
Methyl Thiazolyl-Diphenyl-Tetrazolium Bromide (MTT)
Personalized Cytometric Profiling.

REFERENCES:

  1. American Association of Health Plans (AAHP) “In Vitro Chemosensitivity Testing” AAHP’s MedFlash Special Issue, (05/02).
  2. American Society of Clinical Oncology (ASCO) Clinical Practice Guideline Update on the Use of Chemotherapy Sensitivity and Resistance Assays 2011, accessed at asco.org 09/21/16.
  3. Blue Cross Blue Shield Association Medical Policy “In Vitro Chemoresistance and Chemosensitivity Assays” 2.03.01, 07/16.
  4. Blue Cross Blue Shield Association TEC Assessment “Chemotherapy Sensitivity and Resistance Assays” (10/02), Tab 12.
  5. Blue Cross Blue Shield Association TEC Assessment “Chemotherapy Sensitivity and Resistance Assays” (11/00), Tab 11.
  6. Blue Cross Blue Shield Association TEC Assessment “Nonclonogenic Cytotoxic Drug Resistance Assay” (10/95), Tab 22.
  7. Burstein HJ, et al, American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Chemotherapy Sensitivity and Resistance Assays, JCO.2011. 36.0354 accessed at asco.org 12/27/12.
  8. Centers for Medicare & Medicaid Services (CMS), NCD for Human Tumor Stem Cell Drug Sensitivity Assays (190.7), 07/96, accessed at cms.gov 09/21/16.
  9. ClinicalTrials.gov, Adjuvant Chemotherapy Based on the Adenosine Triphosphate Tumor Chemosensitivity Assay for Hepatocellular Carcinoma After Liver Transplantation, sponsored by Zhejiang University, accessed 09/21/16.
  10. ClinicalTrials.gov, High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia, sponsored by University of Washington, accessed 09/21/16.
  11. ClinicalTrials.gov, Biomarker Study of Chemotherapy Resistance and Outcomes in Samples From Older Patients With Acute Myeloid Leukemia, sponsored by Eastern Cooperative Oncology Group, accessed 04/15/14.
  12. ClinicalTrials.gov Randomized Trial on Chemosensitivity Testing in Advanced Primary Ovarian Carcinoma (Phase III), sponsored by Swiss Group for Clinical Cancer Research, accessed 01/07/08.
  13. ClinicalTrials.gov, ChemoFx® PRO- a Post Market Data Collection Study Utilizing Physician Reported Outcomes, sponsored by Precision Therapeutics, accessed 12/15/10.
  14. ClinicalTrials.gov, Clinical Trial of Chemosensitivity Test, sponsored by Japan Clinical Cancer Research Organization, accessed 01/05/10.
  15. ClinicalTrials.gov, Demographics, Clinical Outcomes, and Physician Attitudes in Patients Who Have Received The MiCK Assay (CorrectChemo), sponsored by DiaTech Oncology, accessed 04/21/15.
  16. ClinicalTrials.gov, Prediction of Response to Neoadjuvant Chemotherapy in Women with Operable Breast Cancer (PT-304), sponsored by Precision Therapeutics, accessed 12/15/10.
  17. ClinicalTrials.gov, Preoperative Chemosensitivity Testing to Predict Treatment Benefit in Adjuvant Stage III Colon Cancer (PePiTA), sponsored by Jules Bordet Institute, accessed 01/05/10.
  18. ClinicalTrials.gov, Retrospective Case Study Examining Patient Outcomes Compared to the ChemoFx Assay in Endometrial Cancer Patients, sponsored by Precision Therapeutics, accessed 12/15/10.
  19. ClinicalTrials.gov, Retrospective Case Study to Validate Existing Chemoresponse Marker Test in Ovarian, Peritoneal or Fallopian Cases, sponsored by precision Therapeutics, accessed 12/15/10.
  20. ClinicalTrials.gov. Accuracy of the chemoFx Chemoresponse Assay in Patients with Recurrent Ovarian, Peritoneal, or Fallopian Tube Cancer, sponsored by Precision Therapeutics, accessed on 01/20/09.
  21. ClinicalTrials.gov. Chemotherapy Drug Sensitivity Microculture (MiCK) Assay for Apoptosis, sponsored by DiaTech Oncology, accessed 01/05/10.
  22. ClinicalTrials.gov. Use of the MiCK Assay for Apoptosis to Predict Complete Remission in Acute Myeloid Leukemia, sponsored by DiaTech Oncology and Vanderbilt University, accessed 01/05/10.
  23. Cree IA, Kurbacher CM, Lamont A, et al, A Prospective Randomized Controlled Trial of Tumour Chemosensitivity Assay Directed Chemotherapy Versus Physician’s Choice in Patients with Recurrent Platinum-resistant Ovarian Cancer, Anticancer Drugs, 2007 Oct; 18(9): 1093-101.
  24. ECRI Custom Hotline Response. In Vitro Chemosensitivity Assays for Predicting Ovarian Cancer Response to Chemotherapy, (02/05).
  25. First Coast Service Options, Inc (FCSO), LCD for Noncovered Services (L33777), 07/25/16.
  26. HAYES Medical Technology Directory “In Vitro Chemosensitivity Assays in Cancer Treatment” (INVI603.06, 05/00) 02/03, (update 06/06).
  27. HAYES Medical Technology Directory “In Vitro Extreme Drug Resistance Assays in Cancer Treatment” (INVI603.07, 05/00), (update 03/05).
  28. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology™, Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer, Version 1.2016.
  29. Schrag D, Garewal HS, Burstein HJ et al. American Society of Clinical Oncology Technology Assessment: Chemotherapy Sensitivity and Resistance Assays. Journal of Clinical Oncology 2004; 22(17): 3631-3638, accessed at asco.org on 02/08/10.
  30. Sorlie T, Perou CM, Fan C, et al, Gene Expression Profiles Do Not Consistently Predict the Clinical Treatment Response in Locally Advanced Breast Cancer, Mol Cancer Ther. 2006 Nov; 5(11): 2914-8.
  31. Tanigawa N, Yamaue H, Ohyama S, et al. Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial). Gastric Cancer. Apr 2016;19(2):350-360.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Medical Policy & Coverage Committee on 10/27/16.

GUIDELINE UPDATE INFORMATION:

12/15/02

Reformat, review & revision of original Medical Coverage Guideline (09/94).

06/15/03

Revised billing/coding information section; deleted CPT codes: 87230, 88-104, 305, 313, 358, and 89050.

06/15/04

Scheduled review, no revisions.

03/15/05

Scheduled review, no change in coverage statement. Revised description section. Format change, reimbursement information section.

03/15/06

Annual review; investigational status maintained.

03/15/07

Scheduled review; no change in coverage statement; references and Internet links updated.

06/15/07

Reformatted guideline.

03/15/08

Annual review: position statement maintained, description section updated, references updated.

03/15/09

Annual review: position statement maintained and references updated.

03/15/10

Annual review: position statement maintained; description section and references updated.

02/15/11

Annual review: position statement maintained and references updated.

09/15/12

Annual review; position statement maintained and references updated.

02/15/13

Revision; position statement, title, description section, and references updated.

08/15/13

Annual review; position statement maintained, program exception and references updates.

06/15/14

Annual review; position statement maintained and references updated.

06/15/15

Annual review; position statement maintained and references updated.

01/01/16

Annual HCPCS/CPT update; codes 81535 and 81536 added.

11/15/16

Revision; description, position statement, and references updated.

Date Printed: June 23, 2017: 11:44 AM