Interim PET Scanning in Oncology to Detect Early Response During Treatment

POLICY NUMBER

A.6.01.51

DESCRIPTION

Positron emission tomography (PET) scanning has many established roles in oncology. One potential use of PET scanning is to assess treatment response early in the course of therapy, with the intent of potentially altering the regimen based on PET scan results. While several types of PET scanning are used for interim detection of cancer, this policy refers to fluorine 18 fluorodeoxyglucose positron emission tomography (FDG-PET) unless otherwise noted.

Positron Emission Tomography

Positron emission tomography (PET) scans are based on the use of positron-emitting radionuclide tracers coupled to other molecules, such as glucose, ammonia, or water. The radionuclide tracers simultaneously emit two high-energy photons in opposite directions that can be simultaneously detected (referred to as coincidence detection) by a PET scanner, which comprises multiple stationary detectors that encircle the region of interest. A variety of tracers are used for PET scanning, including oxygen 15, nitrogen 13, carbon 11, and fluorine 18. The radiotracer most commonly used in oncology imaging has been fluorine 18, coupled with deoxyglucose to form fluorodeoxyglucose (FDG), which has a metabolism related to glucose metabolism. Fluorodeoxyglucose has been considered potentially useful in cancer imaging because tumor cells show increased metabolism of glucose.

This policy focuses on the use of PET to determine early treatment response for cancer, that is, assessment of therapy response during cancer treatment. The purpose of the PET scan at this particular interval is to determine whether the treatment should be maintained or changed. Such a treatment strategy has been called "risk-adapted" or "response-adapted" treatment. This policy addresses detecting early response during short-term therapy (eg, during cycle(s) of chemotherapeutic agents and/or a course of radiotherapy) and not responding during the use of long-term agents, such as tamoxifen.

The technique of using PET for early treatment response assessment involves comparing PET images before treatment and at some interval after the initial course of treatment. Many intervals have been used in various studies, and there appears to be no standard interval. Comparison of the pre-treatment and mid-treatment PET images can either be performed qualitatively or quantitatively. If a quantitative technique is used, the most common quantity measure is the standardized uptake value, calculated for a specific region of the image. Various methods are used to compare standardized uptake values between two images, and a specific cut-off value is selected to determine whether the patient is responding to therapy. A change in standardized uptake value between 40% and 60% has often been used in studies of early treatment response. Other metabolic parameters measured are total lesion glycolysis and metabolic tumor volume.

In 2009, Hillner and colleagues published results of a survey of physicians who had registered patients in the National Oncologic PET Registry, assessing the impact of PET on clinical management decisions for their patients with cancer. PET Scans were most frequently ordered for patients with ovarian cancer (14%), followed by pancreatic cancer (8%), non-small-cell-lung cancer (7%), and small-cell lung cancer (7%). Physicians considered the patients' prognoses as better (42%), unchanged (31%), or worse (26%) compared with the prognosis assessment before receiving information from PET. Physicians reported changing the management plan (switching therapy, adjusting the dose or duration of therapy, or switching to observation or supportive care) in 41% of their patients whose prognosis assessment was better based on PET results, in 35% of patients whose prognosis did not change based on PET results, and in 79% of patients whose prognosis was worse based on PET results.

Use of interim PET to guide therapy decisions is to be distinguished from uses of PET in the initial diagnosis and staging of cancer and other uses after treatment, such as routine surveillance, detection of progression, or recurrence. This use alsodiffers from what has been called "response assessment" or "treatment response" in some reports, which refers to imaging done after completion of therapy for prognosis and future treatment planning. Some differentiate between PET during and after treatment by referring to PET during cancer treatment as "interim treatment response" or "interim staging" and PET at the conclusion of treatment as "restaging."

A number of PET scan platforms have been cleared by the U.S. Food and Drug Administration (FDA) through the 510(k) process since the Penn-PET scanner was approved in 1989. These systems are intended to aid in detecting, localizing, diagnosing, staging, and restaging of lesions, tumors, disease, and organ function for the evaluation of diseases and disorders such as, but not limited to, cardiovascular disease, neurologic disorders, and cancer. The images produced by the system can aid in radiotherapy treatment planning and interventional radiology procedures.

PET radiopharmaceuticals have been evaluated and approved as drugs by the FDA for use as diagnostic imaging agents. These radiopharmaceuticals are approved for specific conditions. In December 2009, the FDA issued guidance for Current Good Manufacturing Practice for PET drug manufacturers and, in August 2011, issued similar Current Good Manufacturing Practice guidance for small businesses compounding radiopharmaceuticals. An additional final guidance document issued in December 2012 required all PET drug manufacturers and compounders to operate under an approved new drug application, abbreviated new drug application, or investigational new drug application, by December 12, 2015.

The table below lists some of the radiopharmaceuticals granted FDA approval for use with PET for oncologic-related indications.

Radiopharmaceuticals Approved for Use With PET for Carcinoma-Related Indications

CT: computed tomography; ER: estrogen receptor; MRI: magnetic resonance imaging; NA: not applicable; NDA: new drug application; NETs: neuroendocrine tumors; PET: positron emission tomography; PSA: prostate-specific antigen; PSMA: prostate-specific membrane antigen. Indications for Oncological Applications of PET Scanning are addressed in a separate policy.Indications for Miscellaneous (Noncardiac, Nononcologic Applications of Fluorodeoxyglucose F 18 Positron Emission Tomography are addressed in a separate policy.Indications for Cardiac Applications of PET Scanning are addressed in a separate policy.

POLICY

The use of interim fluorine 18 fluorodeoxyglucose positron emission tomography scans to determine response to tyrosine kinase inhibitor treatment in individuals with gastrointestinal stromal tumors is considered medically necessary.

The use of PET scans to determine early response to treatment (PET scans done during a planned course of chemotherapy and/or radiotherapy) in individuals with gastrointestinal stromal tumors on palliative or adjuvant therapy, as well as all other cancers, is considered investigational.

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member’s specific benefit plan language.

There is no specific coding for PET scans to determine early response to treatment. The CPT codes for PET or PET/CT imaging (78811-78816) would be used.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

5/20/2009: Policy added.

7/16/2009: Approved by Medical Policy Advisory Committee (MPAC).

11/24/2009: Policy Description Section updated with links to related policies, Policy Exceptions Section revised to include FEP verbiage.

02/23/2011: Policy reviewed; no changes.

08/11/2011: Policy reviewed; no changes.

09/27/2012: Policy reviewed; no changes.

10/22/2013: Policy reviewed; no changes.

10/10/2014: Policy title changed from "PET Scanning in Oncology to Detect Early Treatment Response" to "Interim PET Scanning in Oncology to Detect Early Response During Treatment." Policy reviewed; description updated. Policy statement updated to add that PET scans done during a planned course of chemotherapy and/or radiation therapy is considered investigational.

07/30/2015: Code Reference section updated for ICD-10.

11/04/2015: Policy description updated regarding devices. Policy statement unchanged. Policy guidelines section updated to add investigative definition.

05/31/2016: Policy number A.6.01.51 added.

10/13/2016: Policy description updated regarding devices. Policy statement updated to change "radiation therapy" to "radiotherapy."

04/09/2018: Policy description updated regarding FDA-Approved PET radiopharmaceuticals. Added the following policy statement: The use of interim fluorodeoxyglucose positron emission tomography scans to determine response to tyrosine kinase inhibitor treatment in patients with gastrointestinal stromal tumors is considered medically necessary. Investigational statement regarding the use of PET scans to determine early response to treatment updated to include patients with gastrointestinal stromal tumors on palliative or adjuvant therapy, as well as other cancers, as investigational. Code Reference section updated to move CPT codes 78812 and 78815 from the investigational codes table to the medically necessary codes table. Added ICD-10 diagnosis codes C49.A0 - C49.A9.

10/05/2018: Medically necessary policy statement updated to add "fluorine 18."

10/24/2019: Policy reviewed; no changes.

10/15/2020: Policy description updated regarding radiopharmaceuticals approved for use with PET for carcinoma-related indications. Policy statements unchanged.

12/22/2020: Code Reference section updated to add new HCPCS code A9591, effective 01/01/2021.

01/10/2022: Policy description updated regarding radiopharmaceuticals approved for use with PET for carcinoma-related indications. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

12/02/2022: Policy reviewed. Policy statements updated to change "patients" to "individuals."

10/12/2023: Policy reviewed; no changes.

11/19/2024: Policy reviewed; no changes.

SOURCE(S)

Blue Cross & Blue Shield Association Policy # 6.01.51

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

Investigational Codes

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