Lung Imaging Fluorescence Endoscopy (LIFE)

Number: 0581

Policy

Aetna considers lung imaging fluorescence endoscopy (LIFE) medically necessary to enhance the physician's ability to detect and biopsy abnormal bronchial tissue suspicious for pre-cancerous lesions, carcinomas in-situ, and early bronchogenic carcinomas in any of the following groups:

1. Members with known or previously diagnosed lung cancer; or

2. Members with suspected lung cancer including:

   1. Members suspected of having lung cancer because of clinical symptoms such as positive sputum cytology, hemoptysis, unresolved pneumonia, persistent cough or positive X-ray; or
   2. Members with a previously resected Stage I lung cancer, with no evidence of metastatic disease, who are at risk for secondary disease.

Aetna considers LIFE experimental and investigational for other indications because its clinical value for indications other than the ones listed above has not been established.

Aetna considers the use of point laser Raman spectroscopy to a combined white light bronchoscopy and autofluorescence bronchoscopy for detection of pre-neoplastic lesions experimental and investigational because the effectiveness of this approach has not been established.

Background

In the treatment of lung cancer, the best outcome is achieved when the lesion is detected and localized in the pre-invasive stage.  To date, conventional white-light bronchoscopy has been inadequate for the identification and localization of many early bronchogenic carcinomas, carcinomas in situ (CIS), and pre-cancerous dysplasias because these lesions may exhibit little visual difference from normal tissue when examined with white light.

Recently, the light imaging fluorescence endoscope (LIFE, Xillix Technology, Vancouver, BC) has been approved by the Food and Drug Administration and is now in routine use worldwide at 35 centers.  The LIFE system has been developed based on the principle of autofluorescence, that is, abnormal tissues have the natural ability to fluoresce when exposed to a specific wavelength of light.  The LIFE system utilizes a blue laser light transmitted through a flexible fiberoptic bronchoscope to elicit autofluorescence, which is then projected on to a video screen.  Real-time differentiation of normal bronchial mucosa from dysplastic or carcinomatous mucosa guides the bronchoscopist's biopsies.  Clinical studies have shown that autofluorescence bronchoscopy, when used in conjunction with standard white-light bronchoscopy, increases the detection rate of CIS and moderate to severe dysplasias by 50 %, as compared to white-light bronchoscopy alone.

Note: LIFE is only indicated for use in conjunction with white-light bronchoscopy using an Olympus BF-20D flexible fiber optic bronchoscope and should not be used in combination with photosensitizing agents.  LIFE is restricted by Federal law to be used only by physicians who have completed appropriate training in flexible fiber optic bronchoscopy and who have been trained in the use of the LIFE device.

In a prospective, multi-center, comparative, single-arm trial, Edell et al (2009) evaluated the benefit of using a new fluorescence-reflectance imaging system, Onco-LIFE, for the detection and localization of intra-epitheal neoplasia and early invasive squamous cell carcinoma.  A secondary objective was to evaluate the potential use of quantitative image analysis with this device for objective classification of abnormal sites.  Subjects for this study were aged 45 to 75 years and either current or past smokers of more than 20 pack-years with airflow obstruction, forced expiratory volume in 1 second/forced vital capacity less than 75 %, suspected to have lung cancer based on either sputum atypia, abnormal chest roentgenogram/chest computed tomography, or patients with previous curatively treated lung or head and neck cancer within 2 years.  The primary endpoint of the study was to determine the relative sensitivity of white light bronchoscopy (WLB) plus autofluorescence-reflectance bronchoscopy compared with WLB alone.  Bronchoscopy with Onco-LIFE was carried out in 2 stages.  The first stage was performed under white light and mucosal lesions were visually classified.  Mucosal lesions were classified using the same scheme in the second stage when viewed with Onco-LIFE in the fluorescence-reflectance mode.  All regions classified as suspicious for moderate dysplasia or worse were biopsied, plus at least 1 non-suspicious region for control.  Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the endoscopic findings.  Positive lesions were defined as those with moderate/severe dysplasia, CIS, or invasive carcinoma.  A positive patient was defined as having at least 1 lesion of moderate/severe dysplasia, CIS, or invasive carcinoma.  Onco-LIFE was also used to quantify the fluorescence-reflectance response (based on the proportion of reflected red light to green fluorescence) for each suspected lesion before biopsy.  There were 115 men and 55 women with median age of 62 years.  A total of 776 biopsy specimens were included; 76 were classified as positive (moderate dysplasia or worse) by pathology.  The relative sensitivity on a per-lesion basis of WLB + FLB versus WLB was 1.50 (95 % confidence interval [CI]: 1.26 to 1.89).  The relative sensitivity on a per-patient basis was 1.33 (95 % CI: 1.13 to 1.70).  The relative sensitivity to detect intra-epithelial neoplasia (moderate/severe dysplasia or CIS) was 4.29 (95 % CI: 2.00 to 16.00) and 3.50 (95 % CI: 1.63 to 12.00) on a per-lesion and per-patient basis, respectively.  For a quantified fluorescence reflectance response value of more than or equal to 0.40, a sensitivity and specificity of 51 % and 80 %, respectively, could be achieved for detection of moderate/severe dsyplasia, CIS, and micro-invasive cancer.  The authors concluded that using autofluorescence-reflectance bronchoscopy as an adjunct to WLB with the Onco-LIFE system improves the detection and localization of intra-epitheal neoplasia and invasive carcinoma compared with WLB alone.  The use of quantitative image analysis to minimize inter-observer variation in grading of abnormal sites should be explored further in future prospective clinical trial.

According to available literature, LIFE is considered medically inappropriate for any of the following groups:

1. Persons in whom white light bronchoscopic examination is contraindicated including:

   1. Persons with known bleeding disorder or members on anticoagulant therapy;
   2. Persons with uncontrolled hypertension (systolic pressure greater than 200 mm Hg, diastolic pressure greater than 120 mm Hg);
   3. Persons with unstable angina;
   4. Persons with white blood count less than 2,000 cells/microliter (ul) or greater than 20,000 cells/ul and/or platelet count less than 50,000/mm3.
       

2. Persons in whom fluorescence examination is contraindicated including:

   1. Persons who are on, or have received chemo-preventive drugs (e.g., retinoic acid) within 3 months prior to the procedure;
   2. Persons who have received cytotoxic chemotherapy agents systemically within 6 months prior to the procedure;
   3. Persons who have received fluorescent photosensitizing agents (hematoporphoryn derivatives) within 3 months prior to the procedure;
   4. Persons who have received ionizing radiation treatment to the chest within 6 months prior to the procedure.

Short and colleagues (2011) stated that pre-neoplastic lesions of the bronchial tree have a high probability of developing into malignant tumors.  Currently, the best method for localizing them for further treatment is a combined WLB and autofluorescence bronchoscopy (AFB) (WLB + AFB).  The average specificity from large clinical trials for this combined detection method is approximately 60 %, leading to many false-positives.  In a pilot study, these researchers examined if adding point laser Raman spectroscopy (LRS) to a WLB + AFB has the potential to improve the specificity of pre-neoplastic lesion detection and what the implication is to the detection sensitivity.  An LRS system was developed to collect real-time, in-vivo lung spectra with a fiber optic catheter passed down the instrument channel of a bronchoscope.  WLB + AFB imaging modalities were used to identify lesions from 26 subjects, from which 129 Raman spectra were measured.  Multi-variate statistical analyses were performed on the spectra with a leave-one-out cross-validation.  Clear in-vivo Raman spectra were obtained in 1 second.  The location of individual Raman peaks in the spectra correlated well with the known positions of Raman peaks generated by lipids, proteins, and water molecules.  Pre-neoplastic lesions were detected with a sensitivity of 96 % and a specificity of 91 %.  The authors concluded that adding point LRS analysis to WLB + AFB imaging has the ability to detect pre-neoplastic lesions in real time with high sensitivity and specificity.  They stated that the use of LRS has great potential for substantially reducing the number of false-positive biopsies associated with WLB + AFB with very little reduction in the detection sensitivity.  These preliminary findings need to be validated by well-designed studies.

An UpToDate review on "Screening for lung cancer" (Deffebach and Humphrey, 2014) states that "Non-radiographic technologies, including identification of molecular and protein-based tumor biomarkers, may also contribute to the early detection of lung cancer.  Detection and treatment of small lung tumors (prior to radiographic visualization) may produce superior outcomes, though the possibility of lead-time and other types of bias influencing the assessment of these technologies is great.  Outcome benefits must be thoroughly investigated prior to their widespread use …. Technologies under investigation include fluorescence bronchoscopy".  Furthermore, an UpToDate review on "Fluorescence bronchoscopy" (Banerjee, 2014) states that "An important limitation of autofluorescence bronchoscopy is that false positive results are common.  The impact of autofluorescence bronchoscopy on clinical outcomes, such as mortality, is unknown because it has not been well studied".

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
Other CPT codes related to the CPB:
31622	Bronchoscopy, rigid or flexible, with or without fluoroscopic guidance; diagnostic, with or without cell washing (separate procedure)
31623	with brushing or protected brushings
31624	with bronchial alveolar lavage
31625	with bronchial or endobronchial biopsy(s), single or multiple sites
31628	with transbronchial lung biopsy(s), single lobe
31629	with transbronchial needle aspiration biopsy(s), trachea, main stem and/or lobar bronchus(i)
31630	with tracheal/bronchial dilation or closed reduction of fracture
31631	with placement of tracheal stent(s) (includes tracheal/bronchial dilation as required)
+ 31632	with transbronchial lung biopsy(s), each additional lobe (List separately in addition to code for primary procedure)
31633	with transbronchial needle aspiration biopsy(s), each additional lobe (List separately in addition to code for primary procedure)
31635	with removal of foreign body
31636	with placement of bronchial stent(s) (includes tracheal/bronchial dilation as required), initial bronchus
+ 31637	each additional major bronchus stented (List separately in addition to code for primary procedure)
31638	with revision of tracheal or bronchial stent inserted at previous session (includes tracheal/bronchial dilation as required)
31640	with excision of tumor
ICD-10 codes covered if selection criteria are met (not all-inclusive):
C34.00 - C34.92	Malignant neoplasm of bronchus and lung
C78.00 - C78.02	Secondary malignant neoplasm of lung
D02.20 - D02.22	Carcinoma in situ of bronchus and lung
D14.30 - D14.32	Benign neoplasm of bronchus and lung
D38.1	Neoplasm of uncertain behavior of trachea, bronchus, and lung
J10.00 - J10.08 J11.00 - J11.08 J12.0 - J18.1 J18.8 - J18.9	Pneumonia
R04.2, R04.9	Hemoptysis, unspecified
R04.81	Acute idiopathic pulmonary hemorrhage in infants [AIPHI]
R04.89	Hemorrhage from other sites in respiratory passages
R05	Cough
R84.5	Abnormal microbiological findings in specimens from respiratory organs and thorax [positive culture findings]
R91.1 - R91.8	Abnormal findings on diagnostic imaging of lung
R94.2	Abnormal results of pulmonary function studies
Z85.118	Personal history of other malignant neoplasm of bronchus and lung

The above policy is based on the following references: