Margenza may be considered medically necessary in patients 18 years of age or older for the treatment of metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 regimens, and if the conditions indicated below are met.

Monjuvi may be considered medically necessary in patients 18 years of age or older for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT), and if the conditions indicated below are met.

Rybrevant may be considered medically necessary in patients 18 years of age or older for the treatment of with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations and if the conditions indicated below are met.

Initiation of Ublituximab-xiiy (Briumvi) meets the definition of medical necessity when all the criteria below is met.

Initiation of Imjudo meets the definition of medical necessity when used to treat the established indications and the specific criteria below are met.

Initiation of Teclistamab (Tecvayli) meets the definition of medical necessity when all the criteria below are met.

Enjaymo may be considered medically necessary in adult patients for the of hemolysis in adults with cold agglutinin disease (CAD).

Opdualag may be considered medically necessary in patients 12 years of age or older at least 40 kg for the treatment of adult and pediatric patients with unresectable or metastatic melanoma.

Xenopozyme may be considered medically necessary in adult and pediatric patients for the treatment of non-central nervous system (non-CNS) manifestations of ASMD.

Initiation of Elahere meets the definition of medical necessity when used to treat the following indication and the specific criteria below are met.

Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen.» Rituximab binds specifically to the antigen CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein with a molecular weight of approximately 35 kD located on pre-B and mature B lymphocytes. The antigen is expressed on > 90% of B-cell Non-Hodgkin’s Lymphomas (NHL), but the antigen is not found on hematopoietic stem cells, pro-B-cells, normal plasma cells or other normal tissues. B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In Non-Hodgkin’s Lymphoma (NHL) patients, administration of rituximab resulted in depletion of circulating and tissue-based B cells. In Wegeners Granulomatosis with Polyangiitis and Microscopic Polyangiitis patients, peripheral blood CD19 B-cells depleted to less than 10 cells/µl following the first two infusions of rituximab, and remained at that level in most (84%) patients through Month 6. By Month 12, the majority of patients (81%) showed signs of B-cell return with counts >10 cells/µL.

Trastuzumab is a monoclonal antibody, one of a group of drugs designed to attack specific cancer cells.

Trastuzumab – Trastuzumab Biologics
Trastuzumab’s targets are cancer cells that overexpress an oncogene called HER2 or HER2/neu, which occurs in high numbers in about 25 to 30 percent of breast cancers. According to the National Comprehensive Cancer Network (NCCN), breast cancers can be categorized as being HER2 positive or HER2 negative. HER2-positive breast cancer is faster growing and considered more aggressive. Studies indicate that the drug trastuzumab (Herceptin) is effective in treatment of HER2-positive early stage breast cancer and HER2-positive metastatic breast cancer. Trastuzumab is not effective in the treatment of HER2-negative breast cancers.

Pegfilgrastim is a colony stimulating factor (CSF) that acts on hematopoietic cells by binding to specific cell surface receptors thereby, stimulating proliferation, differentiation, commitment, and end cell functional activation.

History/Background and/or General Information
Pegfilgrastim is approved by the Food and Drug Administration to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Prophylactic use of pegfilgrastim in patients undergoing chemotherapy reduces the risk of febrile neutropenia and infections. Prophylactic therapy can be considered for patients receiving myelosuppressive chemotherapy if the risk of febrile neutropenia is 20% or greater.
Pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf are leukocyte growth factors indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti- cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf are biosimilar* to pegfilgrastim.
*Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information).

Bevacizumab is a humanized monoclonal antibody directed against Vascular Endothelial Growth Factor A (VEGF-A). Vascular Endothelial Growth Factors (VEGF) and their receptors (VEGF-R) contribute to the tumor growth and to the metastasis through the promotion of the angiogenesis.

Off-label non-oncologic uses of Bevacizumab are not discussed in this medical policy.

G-CSF is classified as a recombinant hematopoietic stimulant. This is not a cancer chemotherapy agent. It is a class II hematopoietic growth factor which acts on progenitor cells capable of forming a single differentiated cell type, the neutrophilic granulocyte, and is thus lineage-specific.

History/Background and/or General Information
Pegfilgrastim is approved by the Food and Drug Administration to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Prophylactic use of pegfilgrastim in patients undergoing chemotherapy reduces the risk of febrile neutropenia and infections. Prophylactic therapy can be considered for patients receiving myelosuppressive chemotherapy if the risk of febrile neutropenia is 20% or greater.
Pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf are leukocyte growth factors indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti- cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf are biosimilar* to pegfilgrastim.
*Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information).

Somatuline® Depot; Lanreotide may be considered medically necessary in patients 18 years of age or older and patient has not received a long-acting somatostatin analogue (e.g., Octreotide LAR depot, Lanreotide SR, Lanreotide auto-gel, pasireotide LAR depot, etc.) within the last 4 weeks; AND

Acromegaly1,2,5,6

Patient’s diagnosis is confirmed by elevated (age-adjusted) or equivocal serum IGF-1 as well as inadequate suppression of growth hormone (GH) after a glucose load; AND
Patient has documented inadequate response to surgery and/or radiotherapy or it is not an option for the patient; AND
Patient’s tumor has been visualized on imaging studies (i.e., MRI or CT-scan); AND
Baseline GH and IGF-1 blood levels (renewal will require reporting of current levels); AND
Will not be used in combination with oral octreotide

Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) 1,2

Patient has unresectable, locally advanced or metastatic disease; AND
Patient has non-functioning tumors without hormone-related symptoms; AND
Patient has well or moderately differentiated disease

Carcinoid Syndrome1,2,3

Patient has documented neuroendocrine tumors with a history of carcinoid syndrome
(flushing and/or diarrhea); AND

Used to reduce the frequency of short-acting somatostatin analog rescue therapy; OR
Used for treatment and/or control of symptoms

Neuroendocrine and Adrenal Tumors (e.g., GI Tract, Lung, Thymus, Pancreas, and
Pheochromocytoma/Paraganglioma) 1,2,3,8

Used as primary treatment for unresected primary gastrinoma; OR
Used for locoregional unresectable bronchopulmonary or thymic disease as primary therapy or as subsequent therapy if progression on first-line therapy (including disease progression on prior treatment with lanreotide in patients with functional tumors); AND

Used for management of hormone symptoms and/or somatostatin receptor positivedisease determined by imaging (i.e., 68Ga-dotatate imaging PET/CT or PET/MRI or somatostatin receptor scintigraphy); OR

Patient has distant metastatic bronchopulmonary or thymic disease; AND

Used for somatostatin receptor positive disease and/or symptomatic hormonal disease if clinically significant tumor burden and low grade (typical) histology OR evidence of progression OR intermediate grade (atypical histology); AND

Used as primary therapy or as subsequent therapy if progression on first-line therapy (including disease progression on prior treatment with lanreotide in patients with functional tumors); OR

Used for somatostatin receptor positive disease and/or hormonal symptoms if asymptomatic with low tumor burden and low grade (typical) histology; OR
Used for somatostatin receptor positive disease and/or chronic cough/dyspnea that is notresponsive to inhalers with multiple lung nodules or tumorlets and evidence of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH); OR

Used for the management of locoregional advanced or distant metastatic disease of the gastrointestinal tract; AND

Patient is asymptomatic with a low tumor burden; OR
Patient with a clinically significant tumor burden; OR
Patient has disease progression and is not already receiving lanreotide; OR
Patient has disease progression with functional tumors and will be continuing treatment with lanreotide; OR

Used to manage symptoms related to hormone hypersecretion of locoregional neuroendocrine tumors of the pancreas (well differentiated grade 1/2); AND

Patient has gastrinoma, glucagonoma, or VIPoma; OR

Used for tumor control of locoregional advanced and/or distant metastatic neuroendocrine tumors of the pancreas (well differentiated grade 1/2 – Gastrinoma, Glucagonoma, Insulinoma, VIPoma ) [***NOTE: for insulinoma ONLY, patient must have somatostatin-receptor positive disease]; AND

Patient is asymptomatic with a low tumor burden and stable disease; OR
Patient is symptomatic; OR
Patient has a clinically significant tumor burden; OR
Patient has clinically significant progression and is not already receiving lanreotide; OR

Patient has unresectable locally advanced or metastatic neuroendocrine tumors (well differentiated grade 3); AND

Patient has favorable biology (e.g., relatively low Ki-67 [<55%], somatostatin receptorpositive disease); OR Patient has pheochromocytoma or paraganglioma; AND Patient has symptomatic locally unresectable somatostatin receptor-positive disease; OR Patient has distant metastatic disease

Simponi ARIA® (golimumab)  may be considered medically necessary in  patients is at least 18 years of age, unless otherwise specified; for the following diagnosis:

Rheumatoid Arthritis
Psoriatic Arthritis
Ankylosing Spondylitis
Polyarticular Juvenile Idiopathic Arthritis

Stelara® (ustekinumab) may be considered medically necessary if the following conditions are met:

Patient is at least 18 years of age (unless otherwise specified); AND
Physician has assessed baseline disease severity utilizing an objective measure/tool; AND
Patient is up to date with all age-appropriate vaccinations, in accordance with current vaccination guidelines, prior to initiating therapy; AND
Patient has been evaluated and screened for the presence of latent tuberculosis (TB) infection prior to initiating treatment and will receive ongoing monitoring for presence of TB during treatment; AND
Patient does not have an active infection, including clinically important localized infections; AND
Patient will not receive live vaccines during therapy; AND
Patient is not on concurrent treatment with a TNF-inhibitor, biologic response modifier or other non-biologic agent (i.e., apremilast, tofacitinib, baricitinib, upadacitinib, etc.); AND

Adult Plaque Psoriasis (PsO) 1,30,45-48

Documented moderate to severe plaque psoriasis for at least 6 months with at least one of the following:

Involvement of at least 3% of body surface area (BSA); OR
Psoriasis Area and Severity Index (PASI) score of 10 or greater; OR
Incapacitation or serious emotional consequences due to plaque location (i.e., hands, feet, head and neck, genitalia, etc.) or with intractable pruritis; AND

Patient did not respond adequately (or is not a candidate) to a 4 week minimum trial of topical agents (i.e., anthralin, coal tar preparations, corticosteroids, emollients, immunosuppressives, keratolytics, retinoic acid derivatives, and/or vitamin D analogues); AND
Patient did not respond adequately (or is not a candidate) to a 3 month minimum trial of at least one non-biologic systemic agent (i.e., immunosuppressives, retinoic acid derivatives, and/or methotrexate); AND
Patient did not respond adequately (or is not a candidate*) to a 3 month minimum trial of phototherapy (i.e., psoralens with UVA light [PUVA] or UVB with coal tar or dithranol)

Pediatric Plaque Psoriasis (PsO) 1,30,45-49

Patient is at least 6 years of age; AND
Documented moderate to severe plaque psoriasis for at least 6 months with at least one of the following:

Involvement of at least 3% of body surface area (BSA); OR
Psoriasis Area and Severity Index (PASI) score of 10 or greater; OR
Incapacitation or serious emotional consequences due to plaque location (i.e., hands, feet, head and neck, genitalia, etc.) or with intractable pruritis; AND

Patient did not respond adequately (or is not a candidate) to a 4 week minimum trial of topical agents (i.e., anthralin, coal tar preparations, corticosteroids, emollients, immunosuppressives, keratolytics, retinoic acid derivatives, and/or vitamin D analogues); AND
Patient did not respond adequately (or is not a candidate) to a 3 month minimum trial of at least one non-biologic systemic agent (i.e., immunosuppressives, retinoic acid derivatives, and/or methotrexate); AND
Patient did not respond adequately (or is not a candidate*) to a 3 month minimum trial of phototherapy (i.e., psoralens with UVA light [PUVA] or UVB with coal tar or dithranol

Adult Psoriatic Arthritis (PsA) 1,9,33,50

Documented moderate to severe active disease; AND

For patients with predominantly axial disease OR active enthesitis, a trial and failure of at least a 4 week trial of ONE (1) non-steroidal anti-inflammatory agent (NSAID), unless use is contraindicated; OR
For patients with peripheral arthritis or dactylitis, a trial and failure of at least a 3 month trial of ONE (1) oral disease-modifying anti-rheumatic agent (DMARD) such as methotrexate, azathioprine, sulfasalazine, hydroxychloroquine, etc.

Juvenile Psoriatic Arthritis (PsA) 1,51,52

Patient is at least 6 years of age; AND
Documented moderate to severe active polyarticular disease; AND
May be used as a single agent or in combination with methotrexate; AND
Patient has had at least a 1-month trial and failure (unless contraindicated or intolerant) of previous therapy with either oral non-steroidal anti-inflammatory drugs (NSAIDs) OR an oral disease-modifying anti-rheumatic agent (DMARD) (e.g., methotrexate, leflunomide, sulfasalazine, etc.)

Crohn’s Disease 1,10-12,14,18,24

Documented moderate to severely active disease; AND
Documented failure, contraindication, or ineffective response at maximum tolerated doses to a minimum (3) month trial of corticosteroids or immunomodulators (e.g., azathioprine, 6-mercaptopurine, or methotrexate)

Ulcerative Colitis 1,13,19-23,29

Documented moderate to severe active disease; AND

Documented failure, contraindication, or ineffective response at maximum tolerated doses to a minimum (3) month trial of corticosteroids or immunomodulators (e.g., azathioprine, 6-mercaptopurine, or methotrexate)

Management of Immune Checkpoint Inhibitor-Related Diarrhea/Colitis 35,36

Patient has been receiving therapy with an immune checkpoint inhibitor (e.g., nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, etc.); AND

Patient has mild (grade 1) diarrhea or colitis with persistent or progressive symptoms and is lactoferrin/calprotectin positive; OR
Patient has moderate (grade 2) to severe (grade 3-4) diarrhea or colitis related to their immunotherapy and is refractory to infliximab and/or vedolizumab

Infliximab (Remicade) is a tumor necrosis factor α (TNF-α) blocking agent approved by the U.S. Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and ulcerative colitis. Infliximab is also being considered as an off-label treatment for systemic juvenile idiopathic arthritis, select rheumatic and autoimmune conditions, vasculitides, and nonrheumatic musculoskeletal conditions. This evidence review focuses on the off-label p indications.

Endogenous erythropoietin is a glycoprotein hematopoietic growth factor that regulates hemoglobin levels in response to changes in the blood oxygen concentration. Erythropoiesis-stimulating agents (ESAs; eg, epoetin alfa, pegylated epoetin beta, darbepoetin) are produced using recombinant DNA technologies and have pharmacologic properties similar to endogenous erythropoietin. The primary clinical use of ESAs is to treat chronic anemia.

All periodontal treatments need predetermination of benefits and the treatment plan for evaluation, should be submitted to Triple S Salud.

This allow both, the participant and the insured to confirm beforehand the eligibility of the service for the dental coverage, justification of services with supporting documents, the scope of the covered services, the limits, exclusions, to know which are the deductibles and coinsurance applicable under the insured’s contract.

1.   There must be bone integration of the implant, to be able move to the prosthesis phase of crowns, bridges or dentures.

2.   To the insured person that does not have implant coverage; the participant can charge him as a private patient, the implant and all the other steps  included before inserting the crown. (Example: «healing caps», surgeries, analogous and abutments).

3.    In those coverages that do not include the benefit of implants, all necessary procedures as a result of a complication for the implant are excluded.

1. Crowns should be predetermined and are subject to the corresponding coinsurances and caps.

2. The implant where the crown will be inserted, must show radiographic evidence of osteointegration and comply with the most recent standards, established by the dental profession.

3. The number of tooth to be used to identify the place of insertion of the crown over an implant will be the area of the missing tooth replaced by the corresponding implant.

4. The replacement of crowns on implants will be considered for replacement, after 5 years have passed, with a proper justification.

5. Partials and dentures over implants are mutually exclusive and cannot be replaced until 5 years have passed.

6. To construct a complete or partial denture over an implant, it includes all procedures, technique, materials, adjustments, repairs and rebases until 6 months after the date of insertion.

7. A complete or partial denture over implant can only be billed after having been inserted. The billing date must coincide with the date of insertion.

8 For those coverages that do not include the benefit of implants but cover crowns on implants, they must comply with the following condition:

It will be an indispensable requirement that there are natural teeth present at both ends of the toothless area making a conventional fixed bridge a viable alternative (see Table of Dental Coverages for this benefit and know the corresponding coinsurances).

Code D9420 requires predeterminationand the required documents are;

(a)  patient’s diagnostic

(b)  medical condition of the patient

(c)  the reasons that justify  that the patient  receives general anesthesia

(d)  all other information that can help to the determination

The maxillofacial prosthesis services require predetermination.

1. The maxillofacial prosthesis services require predetermination.

2. Procedure codes D5982 and D5986 are considered for payment one per arch every 5 years. All other codes are considered for payment to 1 service every 5 years. Check benefits and coinsurance in the Coverage Table.

3. Codes D5951 and D5952 are considered for payment until 14 years of age.

4. Code D5953 is considered for payment from 14 years of age and older.

1.Requires predetermination.

2.The predetermination must be accompanied by the evaluation and recommendations of the health professional that refers the insured due to the conditions of problems with speech or breastfeeding.

3.It is not recognized for payment for the purpose of closing diastema, except for those coverages that have the benefit of orthodontics.

4.Frenulum that are causing periodontal problems would be covered if have the benefit of periodontal services.

These services are covered for all patients that have a palatal or nasopharyngeal defect that impairs the person’s ability to swallow efficiently or speak clearly. Although surgery is preferred, it is not always feasible because of the person’s age, health complications or anatomical  causes.

The main goal of maxillary obturator (either temporary or permanent) is to close the gap in the palate or the nasopharynx to make swallowing and speaking possible.

This service is considered as surgical guidance and stabilization for orthognathic surgery (surgical splint).

These surgeries may be recognized for payment as long as one of the following criteria is met:

1.       That there is enough functional inability resulting from illness, trauma, congenital or development

anomalies. This functional inability must be directly related to facial skeletal deformities of the maxilla or mandible (that is, other causes have been ruled out) and must include one or more of the following:

a.    Intraoral trauma directly related to malocclusion.

b.    Difficulty in swallowing.

c.     Speech difficulty resulting in unintelligible language, which has not responded to speech therapy.

d.    Documented loss of biting or chewing functions.

e.    Documented constriction of the person’s airway.

2.    Significant Over or Under jet documented by any of the following:

a.    Reverse over jet of 3mm or more, in cases of maxillary deficiency or protruded jaw.

b.    An over jet of 4mm or more in cases of mandible deficiencies.

c.    Open bite of 4mm or more .

d.    Impinging deep bite of 7mm or more.

e.    Less than 8 mm, posterior teeth in functional intercuspation as a result of abnormal growth or development. (As opposed to the loss of teeth in the arch).

3.    Malocclusions not amenable to conventional orthodontic correction.

Diagnostic Procedures

The following diagnostic procedures may be considered medically necessary in the diagnosis of temporomandibular joint disorder (TMJD):

Diagnostic x-ray, tomograms, and arthrograms;

Computed tomography (CT) scan or magnetic resonance imaging (MRI) (in general, CT scans and MRIs are reserved for presurgical evaluations);

Cephalograms (x-rays of jaws and skull);

Pantograms (x-rays of maxilla and mandible).

(Cephalograms and pantograms should be reviewed on an individual basis.)

The following diagnostic procedures are considered investigational in the diagnosis of TMJD:

Electromyography (EMG), including surface EMG;

Kinesiography;

Thermography;

Neuromuscular junction testing;

Somatosensory testing;

Transcranial or lateral skull x-rays; intraoral tracing or gnathic arch tracing (intended to demonstrate deviations in the positioning of the jaw that are associated with TMJD);

Muscle testing;

Standard dental radiographic procedures;

Range-of-motion measurements;

Computerized mandibular scan (measures and records muscle activity related to movement and positioning of the mandible and is intended to detect deviations in occlusion and muscle spasms related to TMJD);

Ultrasound imaging/sonogram;

Arthroscopy of the temporomandibular joint (TMJ) for purely diagnostic purposes;

Joint vibration analysis.

Nonsurgical Treatments

The following nonsurgical treatments may be considered medically necessary in the treatment of TMJD:

Intraoral removable prosthetic devices or appliances (encompassing fabrication, insertion, adjustment);

Pharmacologic treatment (eg, anti-inflammatory, muscle relaxing, analgesic medications).

The following nonsurgical treatments are considered investigational in the treatment of TMJD:

Electrogalvanic stimulation;

Iontophoresis;

Biofeedback;

Ultrasound;

Devices promoted to maintain joint range of motion and to develop muscles involved in jaw function;

Orthodontic services;

Dental restorations/prostheses;

Transcutaneous electrical nerve stimulation;

Percutaneous electrical nerve stimulation;

Acupuncture;

Hyaluronic acid;

Platelet concentrates;

Dextrose prolotherapy.

Botulinum toxin A.

Surgical Treatments

The following surgical treatments may be considered medically necessary in the treatment of TMJD:

Arthrocentesis;

Manipulation for reduction of fracture or dislocation of the TMJ;

Arthroscopic surgery in individuals with objectively demonstrated (by physical examination or imaging) internal derangements (displaced discs) or degenerative joint disease who have failed conservative treatment;

Open surgical procedures (when TMJD results from congenital anomalies, trauma, or disease in individuals who have failed conservative treatment) including, but not limited to, arthroplasties; condylectomies; meniscus or disc plication, and disc removal.

1. That sufficient functional disability be present as a result of disease, trauma, congenital anomalies or developmental dysfunction.  This functional disability must be directly related to a dent maxillofacial (maxilla and mandible) abnormality and must include one or more of the following:

a. Significant intraoral trauma while chewing related to malocclusion. Information should be supplied which indicates the severity and duration of the trauma and the extent of the interruption to daily activities. This may include recurrent damage to the soft tissues of the mouth during mastication, lower incisors injuring the soft tissue of the palate, cheek biting, lip biting, impingement or irritation of buccal or lingual soft tissues of the opposing arch. The injury or damage to soft tissues must be documented by objective findings in the medical record and supported by photos.

b. Speech abnormalities that result in an unintelligible language, which have not responded to speech therapy or frenulectomy.

c. Documented loss of chewing or incisive function.

d. Congenital condition where there are dentomaxillofacial deformities.

2. Significant over or underjet, documented by one of the following:

a. A reverse overjet of 3mm or more, in cases of maxillary deficiency, or mandibular excess.

b. An overjet of 4mm or more, in cases of mandibular deficiency.

c. Open bite of 4mm or more.

d. Deep bite of 7mm or more.

e. Less than six (6) posterior teeth in functional opposition to other teeth as a result of abnormal growth or development (as opposed, to the result of tooth loss in the arch).

The following documents are required to consider the predeterminations of orthodontic services;

1. It must be accompanied with the completed form 193.

2. Lateral cephalometric radiography.

3. Tracing of the cephalometric with the corresponding measurements.

4. Photographs intra and extra oral pre-orthodontics.

5. Report that includes diagnosis (ICD-10) and corresponding CDT code.

6. Study model if necessary.

Viscosupplementation therapy is part of the therapy used in the treatment of osteoarthritis of the knee. Osteoarthritis results from articular cartilage failure due to the complex interplay of genetic, metabolic, biochemical and biomechanical factors with a secondary component of inflammation. In most patients the initiating mechanism is damage to the articular cartilage either as a single large injury or a series of repeated smaller injuries. The primary symptom of osteoarthritis of the knee is pain, however, because cartilage is aneural, significant radiographic findings are often noted in asymptomatic individuals imaged for other reasons.

Germline BRCA1/2 variant analysis for individuals with metastatic castrate-resistant prostate cancer (mCRPC) to select treatment with FDA-approved targeted therapies may be considered medically necessary.

All other uses of germline BRCA1/2 variant analysis to guide prostate cancer targeted therapy are considered investigational.

Somatic testing using tissue biopsy for homologous recombination repair (HRR) gene alterations (BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, and RAD54L) to select treatment for mCRPC with FDA-approved targeted therapies may be considered medically necessary.

All other uses of somatic testing using tissue biopsy for HRR gene alterations to guide prostate cancer targeted therapy are considered investigational.

Somatic testing using circulating tumor DNA testing (liquid biopsy) for BRCA1, BRCA2, and ATM alterations to select treatment for mCRPC with FDA-approved targeted therapies may be considered medically necessary.

All other uses of somatic testing using circulating tumor DNA testing (liquid biopsy) to guide prostate cancer targeted therapy are considered investigational.

Simultaneous testing using liquid and tumor biopsies (outside of paired or concurrent somatic-germline testing) to guide treatment in individuals with prostate cancer is considered investigational (see Policy Guidelines).

Testing for other variants may become available between policy updates.

Germline BRCA1/2 variant analysis may be considered medically necessary for individuals with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer to select treatment with FDA-approved targeted therapies.

Somatic BRCA1/2 variant analysis using tumor tissue may be considered medically necessary for individuals with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer to select treatment with FDA-approved targeted therapies.

All other uses of germline and somatic BRCA1/2 variant analysis to guide targeted therapy for ovarian, fallopian tube, or primary peritoneal cancer are considered investigational.

Homologous recombination deficiency (HRD) analysis of tumor tissue may be considered medically necessary for individuals with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer to select treatment with FDA-approved targeted therapies.

All other uses of HRD testing of tumor tissue to guide targeted therapy for ovarian, fallopian tube, or primary peritoneal cancer are considered investigational.

BRCA1/2 variant analysis using circulating tumor DNA (liquid biopsy) may be considered medically necessary for individuals with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer to select treatment with FDA-approved targeted therapies when tissue-based analysis is not clinically feasible.

All other uses of circulating tumor DNA testing (liquid biopsy) to guide targeted therapy in individuals with ovarian, fallopian tube, or primary peritoneal cancer are considered investigational.

Simultaneous testing using liquid and tumor biopsies (outside of paired or concurrent somatic-germline testing) to guide treatment in individuals with ovarian, fallopian tube, or primary peritoneal cancer is considered investigational (see Policy Guidelines).

Testing for other variants may become available between policy updates.

BRAF V600 Variant Testing

BRAF V600 variant testing of tumor tissue to select individuals for immune checkpoint inhibitor therapy may be considered medically necessary in the following circumstances:

Individuals with unresectable or metastatic melanoma.

AND

The individual does not have any U.S. Food and Drug Administration (FDA)-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label.

Analysis of tumor tissue for the somatic BRAF V600 variant to select individuals for immune checkpoint inhibitor therapy is considered investigational in all other situations.

Mismatch Repair/Microsatellite Instability Testing

Mismatch repair/microsatellite instability (MMR/MSI) testing of tumor tissue to select individuals for immune checkpoint inhibitor therapy may be considered medically necessary in the following circumstances:

Individuals with advanced or metastatic colorectal cancer; OR
Individuals with advanced endometrial carcinoma who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation; OR
Individuals with unresectable or metastatic solid tumors who have progressed following prior treatment and who have no satisfactory alternative treatment options.

AND

The individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label.

Mismatch repair/microsatellite instability testing to select individuals for immune checkpoint inhibitor therapy is considered investigational in all other situations.

Programmed Cell Death Ligand-1 Testing

Programmed cell death ligand protein-1 (PD-L1) testing of tumor tissue to select individuals for immune checkpoint inhibitor therapy may be considered medically necessary in the following circumstances:

Individuals with metastatic non-small cell lung cancer (NSCLC); OR

Individuals with metastatic or unresectable, recurrent head and neck squamous cell carcinomas; OR

Individuals with locally advanced or metastatic esophageal or gastroesophageal junction carcinoma that is not amenable to surgical resection or definitive chemoradiation after 1 or more prior lines of systemic therapy for patients with tumors of squamous cell histology; OR

Individuals with persistent, recurrent, or metastatic cervical cancer; OR

Individuals with locally recurrent unresectable or metastatic hormone receptor-negative/HER2-negative (triple negative) breast cancer.

AND

The individual does not have any FDA-labeled contraindications to the requested agent and the agent is intended to be used consistently with the FDA-approved label.

PD-L1 testing of tumor tissue to select individuals for immune checkpoint inhibitor therapy is considered investigational in all other situations.

Tumor Mutational Burden Testing

Tumor mutational burden (TMB) testing of tumor tissue to select individuals for immune checkpoint inhibitor therapy is considered investigational.

All tests listed in this policy are considered investigational as there is insufficient evidence to determine that the technology results in an improvement in the net health outcome (see Policy Guidelines).

Local infiltration and pudendal blockade are considered part of the management of labor and are included in the code 59410 for vaginal delivery.

Neuraxial analgesia (continuous epidural) is considered for payment in the following situations:

ü Fetal causes (eg, fetal distress, cord prolapses, placental abruption)

ü Maternal causes (eg, maternal cardiovascular disease, maternal respiratory disease, history of malignant hyperthermia, parturient with a high spinal cord injury, when a possible difficulty in intubation is anticipated).

ü Breech fetal presentation

ü Elective application of «forceps»

Single Crowns, inlays or onlays require predetermination and must be accompanied by periapical radiographic images with diagnostic value and a narrative or report informing the clinical and radiographic findings. These procedures are subject to the corresponding coinsurance

All removable dentures; complete or partial, require predetermination in the line of buisiness Advantage and, Comercial line of Buisness  Federal, (D-41). (See dental coverage table for those that do not require predetermination).

All fixed bridges require predetermination. Please refer to the section of Predetermination of Benefits for the requirements related to this process.

Rules and limitations for other fixed partial dentures services:

1.     Code D6940 Stress breaker and D6920, required predetermination and will be considered for payment one by arch every 5 years.

2.     Procedure code D6950 precision attachment requires predetermination and is considered for payment one by quadrant every 5 years.

If it is necessary to make a retreatment before 5 years, a predetermination is required and this must be accompanied by a detailed report of clinical findings and its necessity with pre-operative periapical radiographic image.

1.A history of a surgical code will limit for payment the approval of a second surgical code in a same

quadrant if three years have not passed.

2. Any surgical procedure for cosmetic purposes is excluded for payment.

3.  In those covers that do not include the benefit of implants, all procedures related to the implant are     excluded, such as, and not limited to, bone grafts and membranes in areas of extraction for implants and maintenance of dental implants.

4. Codes D4210 and D4211 are indicated for cases with gingival hyperplasia with none or minimal bone loss and are limited for payment to one of the two services per quadrant every 3 years.

5.  Code D4210 is used when the quadrant contains a minimum of 4 teeth that need surgery. Code D4211 will be used for cases in which it is only necessary to perform surgery in three teeth or less in the same quadrant.

6.  Every predetermination for soft tissue surgery requires a report indicating its necessity. You must include pictures, if they are available, as a diagnostic aid to advise in the case.

7.  The fee for codes D4240, D4241, D4260 and D4261 includes the fee of codes D4341 and D4342 when these are performed in the same quadrant, on the same day.

8.  Code D4245 is limited for payment to one per quadrant for life. A detailed «by report» is required and will not be considered for payment in conjunction with code D7960 if it is performed in the same visit. It will be billed using the quadrant number.

9.  Code D4249 is limited to one payment per tooth per life and will be invoiced using the number of the tooth. The amount paid for codes D4249 in the same      quadrant may not exceed the rate of code D4260.

10.  The rate of code D4249 was included in that of D4260 and D4261 if done in the set in the same affected area of the quadrant.

11.  The following codes are limited to pay one per quadrant every three years: D4210, D4211, D4240, D4241, D4260, D4261, D4270, D4273 and these are        mutually exclusive. The quadrant number was used.

12.  Codes D4263, D4264, D4277 and D4278 are made using the tooth number and will be limited to 1 per tooth per life. X-rays or photographs should be        sent to show the need and any other diagnostic help that may facilitate the evaluation of the case.

13.  Codes D4277 and D4278 on the ADA sheet in the «observation» section should indicate the classification (MILLER).

14.  The codes D4263 and D4264 must indicate the SITE of the bone defect in addition to the number of the tooth.

15.  The codes D4266 and D4267 will be limited to 1 per quadrant every 3 years and is billed using the tooth number.

16.  The codes D4277 and D4278 are mutually exclusive of codes D4270 and D4273.

17.  The following codes will only be considered for payment in type II bifurcations and interproximal infrabony defects. (D4263, D4264, D4266 and D4267).

18.   Gingival grafts are limited for payment to one (1) per quadrant every three years and will be billed using the quadrant number.

The use of genetic testing for the LPA rs3798220 allele (LPA-Aspirin Genotype) is considered investigational in patients who are being considered for treatment with aspirin to reduce the risk of cardiovascular events.

Microarray-based gene expression profile testing for multiple myeloma is considered investigational for all indications.

Genetic testing for BRCA1, BRCA2, and PALB2 variants to guide selection for treatment with platinum-based chemotherapy in previously untreated patients with locally advanced or metastatic pancreatic cancer may be considered medically necessary

Genetic testing for BRCA1 and BRCA2 variants to guide selection for treatment with olaparib (Lynparza) in patients with pancreatic cancer may be considered medically necessary

Genetic testing for ATM, CDK2NA, EPCAM, MMR genes (MLH1, MSH2, MSH6, PMS2), STK11, and TP53 in patients with pancreatic cancer is considered investigational unless the individual meets criteria for testing as specified in another policy (see policy guidelines)

Genetic testing for ATM, BRCA1, BRCA2, CDK2NA, EPCAM, MMR genes (MLH1, MSH2, MSH6, PMS2), PALB2, STK11, and TP53 in asymptomatic individuals at high risk for hereditary pancreatic cancer is considered investigational unless the individual meets criteria for testing as specified in another policy (see policy guidelines)

Measurement of antidrug antibodies in an individual receiving treatment with a biologic agent, either alone or as a combination test, which includes the measurement of serum tumor necrosis factor (TNF) blocking agent levels, is considered investigational.

HLA-DQ2 and HLA-DQ8 testing may be considered medically necessary to rule out celiac disease in:

patients with persistent symptoms despite negative serology and histology; or

patients with discordant serologic and histologic (biopsy) findings.

HLA-DQ2 and HLA-DQ8 testing for celiac disease is considered investigational in all other situations.

Genetic testing for the presence of variants in the SLCO1B1 gene to identify patients at risk of statin-induced myopathy is considered investigational.

Sphenopalatine ganglion blocks are considered investigational for all indications, including but not limited to the treatment of migraines and non-migraine headaches.

SEPT9 methylated DNA testing (eg, ColoVantage®, Epi proColon®) is considered investigational for colorectal cancer screening.

Gene expression profiling (eg, ColonSentry®, BeScreened™-CRC ) is considered investigational for colorectal cancer screening.

Testing for germline BRIP1, RAD51C, and RAD51D variants for ovarian cancer risk assessment in adults may be considered medically necessary when the following criteria are met:

The individual has a diagnosis of epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; AND

The individual has not previously been tested for these gene variants; AND

The individual is thought to be the most informative member of a family (proband) to have genetic testing (see Policy Guidelines); AND

The individual has closely related (first- and/or second-degree) relatives who are considering genetic testing for these gene variants to inform prophylactic decision-making or who have test results that cannot be fully interpreted without testing an affected relative; OR

The individual has not been diagnosed with epithelial ovarian cancer; AND

The individual has any blood relative with a known pathogenic/likely pathogenic germline BRIP1, RAD51C, or RAD51D variant; OR

The individual has a first- or second-degree relative diagnosed with ovarian cancer.a

Testing for germline NBN variants for ovarian cancer risk assessment in adults is considered investigational.

Testing for germline BRIP1, RAD51C, RAD51D, and NBN variants in individuals diagnosed with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer to guide treatment of the diagnosed individual is considered investigational.

Testing for germline BRIP1, RAD51C, and RAD51D variants for ovarian cancer risk in adults who do not meet the criteria above is considered investigational.

a For familial assessment, first- and second-degree relatives are blood relatives on the same side of the family (maternal or paternal):

First-degree relatives: parents, siblings, and children

Second-degree relatives: grandparents, aunts, uncles, nieces, nephews, grandchildren, and half-siblings.

Tumor-informed circulating tumor DNA testing (e.g., Signatera) is considered investigational for all indications.

Germline genetic testing for CDH1 variants to identify individuals with or at risk for hereditary diffuse gastric cancer (HDGC) may be considered medically necessary for individuals meeting the following criteria (see Policy Guidelines):

A diagnosis of diffuse gastric cancer (DGC) before age 50 years; OR

A diagnosis of DGC at any age in individuals of Maori ethnicity, or with a personal or family history of cleft/lip palate; OR

A diagnosis of bilateral lobular breast cancer before age 70 years; OR

Personal or family history of both DGC and lobular breast cancer, one diagnosed before age 70 years; OR

Two 1st- or 2nd-degree relatives (see Policy Guidelines) with a diagnosis of gastric cancer at any age, one DGC; OR

Two 1st- or 2nd-degree relatives (see Policy Guidelines) with a diagnosis of lobular breast cancer before 50 years of age.

Germline genetic testing for CDH1 variants in individuals not meeting the above criteria is considered investigational.

Germline genetic testing for CTNNA1 variants to identify individuals with or at risk for HDGC is considered investigational (see Policy Guidelines).

Acupuncture may be considered medically necessary for treatment of episodic migraines and/or tension-type headaches.

Acupuncture is considered investigational for the treatment of other pain-related conditions including but not limited to:

Low back pain

Shoulder pain

Lateral elbow pain

Carpal tunnel syndrome

Cancer pain in adults

Chronic pain in patients with spinal cord injury

Pain in endometriosis

Pain in rheumatoid arthritis.

Acupuncture is considered investigational for the prevention or treatment of nausea and/or vomiting.

Acupuncture is considered investigational for opioid reduction or cessation in opiate users.

The use of the Presage ST2 Assay to evaluate the prognosis of patients diagnosed with chronic heart failure is considered investigational.

The use of the Presage ST2 Assay to guide management (eg, pharmacologic, device-based, exercise) of patients diagnosed with chronic heart failure is considered investigational.

The use of the Presage ST2 Assay in the post cardiac transplantation period, including but not limited to predicting prognosis and predicting acute cellular rejection, is considered investigational.

The use of the myTAIHEART assay in the post cardiac transplantation period, including but not limited to predicting prognosis and predicting acute cellular rejection, is considered investigational.

The use of circulating tumor DNA and/or circulating tumor cells is considered investigational for all indications reviewed herein (see Policy Guidelines).

Gene expression profiling for uveal melanoma with DecisionDx-UM is medically necessary for patients with primary, localized uveal melanoma.

Gene expression profiling for uveal melanoma that does not meet the above criteria is investigational.

Proteogenomic testing (see Policy Guidelines section) of patients with cancer (including, but not limited to the GPS Cancer test) is considered investigational for all indications.

Genetic testing to establish a genetic diagnosis of a mitochondrial disorder may be considered medically necessary when signs and symptoms of a mitochondrial disorder are present and genetic testing may eliminate the need for muscle biopsy.

Targeted genetic testing for a known familial variant in at-risk relatives may be considered medically necessary as preconceptional carrier testing under the following conditions (see Benefit Application section):

There is a defined mitochondrial disorder in the family of sufficient severity to cause impairment of quality of life or functional status; AND

A variant that is known to be pathogenic for that specific mitochondrial disorder has been identified in the index case.

Genetic testing for mitochondrial disorders is considered investigational in all other situations when the criteria for medical necessity are not met.

Serum biomarker panel testing with proprietary algorithms and/or index scores for the diagnosis of systemic lupus erythematosus and other connective tissue diseases is considered investigational.

Genotyping to determine cytochrome P450 2D6 (CYP2D6) variants is considered investigational for the purpose of managing treatment with tamoxifen for women at high risk for or with breast cancer.

All tests listed in this policy are considered investigational and grouped according to the categories of genetic testing outlined in evidence review 2.04.91:

Testing of an affected (symptomatic) individual’s germline to benefit the individual (excluding reproductive testing)
Diagnostic testing
Prognostic testing
Therapeutic testing
Testing an asymptomatic individual to determine future risk of disease.

Gene expression testing, including but not limited to the Pigmented Lesion Assay, in the evaluation of individuals with suspicious pigmented lesions is considered investigational.

Gene expression testing, including but not limited to the myPath Melanoma test, in the evaluation of individuals with melanocytic lesions with indeterminate histopathologic features is considered investigational.

Gene expression testing, including but not limited to DecisionDx-Melanoma, in the evaluation of individuals with cutaneous melanoma is considered investigational for all indications.

Testing for 1 or more single nucleotide variants to predict an individual’s risk of breast cancer is considered investigational.

The GeneType® breast cancer risk test is considered investigational for all indications, including but not limited to use as a method of estimating individual risk for developing breast cancer.

The use of proteomic testing, including but not limited to the VeriStrat assay, is considered investigational for all uses in the management of non-small-cell lung cancer.

DNA-based prognostic testing for adolescent idiopathic scoliosis is considered investigational.

Assay testing for determining 5-fluorouracil area under the curve in order to adjust 5-fluorouracil dose for individuals with cancer is considered investigational.

Testing for genetic variants in dipyrimidine dehydrogenase (DPYD) or thymidylate synthase (TYMS) genes to guide 5-fluorouracil dosing and/or treatment choice in individuals with cancer is considered investigational.

The use of proteomic testing, including but not limited to the VeriStrat assay, is considered investigational for all uses in the management of non-small-cell lung cancer.

The use of a multibiomarker disease activity score for rheumatoid arthritis (eg, Vectra score) is considered investigational in all situations

El uso de paneles de varios analitos con el análisis algorítmico (MASA) para la predicción de la diabetes tipo 2 no se considera para pago
Directrices de Política
81506: Endocrinología (diabetes tipo 2), ensayos bioquímicos de siete analitos (glucosa, HbA1c, insulina, hs-CRP, la adiponectina, la ferritina, la interleucina-2 alfa del receptor), utilizando suero o plasma, el algoritmo de informes una puntuación de riesgo.
Resumen de la Sección
El PreDx® DRS ha sido probado en 2 cohortes prospectivas diferentes de pacientes, con AUC reportado para la predicción de la diabetes de 0,78 y 0,84, lo que indica una buena precisión en general para predecir la progresión de la diabetes. Se ha evaluado en 1 cohorte EE.UU., pero no de otro modo ha sido probado en una amplia gama de poblaciones de pacientes. Como resultado, hay una cierta incertidumbre en la exactitud predictiva y generalización de la puntuación de riesgo.
La evidencia es insuficiente para determinar la eficacia comparativa de la puntuación de los PreDx® en comparación con otras puntuaciones de riesgo de la diabetes. El único estudio que comparó la puntuación PreDx® con 2 medidas establecidas (Framingham de riesgo de diabetes, San Antonio puntuación de riesgo de la diabetes del corazón) informó que la precisión global, tal como se define por las AUC para predecir la progresión de la diabetes, no difirió significativamente entre las 3 medidas. Un estudio realizado en una cohorte de pacientes de EE.UU. sugirió que la puntuación PreDx® puede predecir mejor la diabetes que varios factores de riesgo individuales solos. Sin embargo, esta evidencia comparativa es incompleta, y se necesitan estudios comparativos más exhaustivos.

Nucleic acid sequencing-based testing of maternal plasma to screen for trisomy 21, 18, and 13 may be considered medically necessary in individuals with singleton pregnancies.

Nucleic acid sequencing-based testing of maternal plasma for fetal sex chromosome aneuploidies is considered investigational.

Nucleic acid sequencing-based testing of maternal plasma for trisomy 21 is considered investigational in individuals with twin or multiple pregnancies.

Nucleic acid sequencing-based testing of maternal plasma for microdeletions is considered investigational.

Nucleic acid sequencing-based testing of maternal plasma for twin zygosity is considered investigational.

Vanadis NIPT of maternal plasma to screen for trisomy 21, 18 and 13 is considered investigational in all situations.

Vistara NIPT of maternal plasma to screen for single-gene disorders is considered investigational in all situations.

Nucleic acid sequencing-based testing of maternal plasma, other than in the situations specified above, is considered investigational.

Chromosomal Microarray Testing

In patients who are undergoing invasive diagnostic prenatal (fetal) testing, chromosome microarray testing may be considered medically necessary as an alternative to karyotyping (see Policy Guidelines).

Single-Gene Disorders

Invasive diagnostic prenatal (fetal) testing for molecular analysis for single-gene disorders may be considered medically necessary when a pregnancy has been identified as being at high risk:

For autosomal dominant conditions, at least one of the parents has a known pathogenic variant.

For autosomal recessive conditions:

Both parents are suspected to be carriers or are known to be carriers, OR

One parent is clinically affected and the other parent is suspected to be or is a known carrier.

For X-linked conditions: A parent is suspected to be or is a known carrier.

AND, ALL of the following are met:

The natural history of the disease is well-understood, and there is a reasonable likelihood that the disease is one with high morbidity in the homozygous or compound heterozygous state, AND

Any variants have high penetrance, AND

The genetic test has adequate sensitivity and specificity to guide clinical decision making and residual risk is understood, AND

An association of the marker with the disorder has been established.

If the above criteria for molecular analysis of single-gene disorders are not met, invasive diagnostic prenatal (fetal) testing is considered investigational.

Next-Generation Sequencing

The use of next-generation sequencing in the setting of invasive prenatal testing is considered investigational.

Genetic testing for macular degeneration is considered investigational.

Genetic testing for facioscapulohumeral muscular dystrophy may be considered medically necessary to confirm a diagnosis in a patient with clinical signs of the disease (see the Policy Guidelines section).

Genetic testing for facioscapulohumeral muscular dystrophy is considered investigational for all other indications.

Plasma-based proteomic screening, including but not limited to BDX-XL2 (Nodify XL2®), in individuals with undiagnosed pulmonary nodules detected by computed tomography is considered investigational.

Gene expression profiling on bronchial brushings, including but not limited to the Percepta® Genomic Sequencing Classifier, in individuals with indeterminate bronchoscopy results from undiagnosed pulmonary nodules is considered investigational.

KIF6 genotyping is considered investigational for predicting cardiovascular risk and/or the effectiveness of statin therapy.

Genetic testing for genes associated with limb-girdle muscular dystrophy to confirm a diagnosis of limb-girdle muscular dystrophy may be considered medically necessary when signs and symptoms of limb-girdle muscular dystrophy are present but a definitive diagnosis cannot be made without genetic testing, and when at least one of the following criteria are met:

Results of testing may lead to changes in clinical management that improve outcomes (eg, confirming or excluding the need for cardiac surveillance); OR

Genetic testing will allow the affected individual to avoid invasive testing, including muscle biopsy.

Genetic testing for genes associated with limb-girdle muscular dystrophy in the reproductive setting may be considered medically necessary when:

There is a diagnosis of limb-girdle muscular dystrophy in one or both of the parents, AND

Results of testing will allow informed reproductive decision making.

Targeted genetic testing for a known familial variant associated with limb-girdle muscular dystrophy may be considered medically necessary in an asymptomatic individual to determine future risk of disease when the following criteria are met:

The individual has a close (ie, first- or second-degree) relative with a known familial variant consistent with limb-girdle muscular dystrophy, AND

Results of testing will lead to changes in clinical management (eg, confirming or excluding the need for cardiac surveillance).

Genetic testing for genes associated with limb-girdle muscular dystrophy may be considered medically necessary in an asymptomatic individual to determine future risk of disease when the following criteria are met:

The individual has a close (ie, first- or second-degree) relative diagnosed with limb-girdle muscular dystrophy whose genetic status is unavailable, AND

Results of testing will lead to changes in clinical management (eg, confirming or excluding the need for cardiac surveillance).

Genetic testing for genes associated with limb-girdle muscular dystrophy is considered investigational in all other situations.

Comprehensive genetic testing for individuals with signs or symptoms of dilated cardiomyopathy, which is considered idiopathic after a negative workup for secondary causes, is considered medically necessary.

Targeted genetic testing for asymptomatic individuals with a first-degree relative who has dilated cardiomyopathy and a known familial variant is considered medically necessary.

Genetic testing for dilated cardiomyopathy is considered investigational in all other situations.

Genetic testing for CHARGE syndrome may be considered medically necessary to confirm a diagnosis in a patient with signs/symptoms of CHARGE syndrome when a definitive diagnosis cannot be made with clinical criteria (see Policy Guidelines section).

Genetic testing for CHARGE syndrome is considered investigational in all other situations.

El uso de genotipificación para 9p21 polimorfismos de nucleótido único (SNPs) no se considera para pago para todos los usos clínicos, incluyendo pero no limitado a la identificación de los pacientes que pueden estar en mayor riesgo de enfermedad cardiovascular o de sus manifestaciones (por ejemplo, infarto de miocardio, accidente cerebrovascular isquémico, enfermedad arterial periférica, la calcificación de las arterias coronarias), o la identificación de pacientes que pueden estar en un mayor riesgo de enfermedad aneurismática (aneurismas aórticos abdominales, aneurismas intracraneales, vasculopatía coroidea polipoidal
Resumen de Evidencia
La asociación de los polimorfismos de un solo nucleótido en el locus 9p21 con la arteria coronaria / enfermedades del corazón (CAD / CHD) los resultados (validez clínica) está bien establecida y consistente en múltiples poblaciones independientes, con evidencia de aumento de la gravedad de los resultados con el aumento de la dosis alelo de riesgo. La validez clínica de la asociación de los polimorfismos 9p21 con accidente cerebrovascular isquémico, aneurismas, u otro trastornos vasculares no esta bien estudiado y es menos seguro. Aunque está claro que polimorfismos 9p21 están asociados con CAD / incidencia de cardiopatía coronaria y los resultados, no se ha podido establecer la utilidad clínica de la determinación del genotipo 9p21. Los estudios no han demostrado de manera concluyente que el genotipado 9p21 mejora significativamente la reclasificación del riesgo después de la clasificación inicial de los factores de riesgo tradicionales o que la adición de genotipado 9p21 a los factores de riesgo tradicionales mejora la evaluación de riesgos. No se identificaron estudios que evalúan si el uso de genotipificación de 9p21se asocia con cambios en el manejo del paciente, las mejoras en los resultados clínicos, o ambas cosas. Por lo tanto, el genotipado de 9p21 para todas las aplicaciones está en fase de investigación.
Información Suplementaria
Guías de Práctica y declaraciones de posición
American College of Cardiology y la American Heart Association
En 2013, el Colegio Americano de Cardiología y la Asociación Americana del Corazón en la Guía de Práctica emitieron directrices para la evaluación del riesgo cardiovascular, que no se refirió a la evaluación de polimorfismos 9p21.62
Evaluación de Aplicaciones Genómicas en la práctica y Grupo de Trabajo de PrevenciónLa Evaluación de Aplicaciones Genómicas en la práctica y Grupo de Trabajo de Prevención (EWG) publicó una recomendación sobre «… el perfil genómico para evaluar el riesgo cardiovascular para mejorar la salud cardiovascular» que incluía una recomen-dación sobre perfiles solos de 9p21 basado en Palomaki et al10 En general, EWG encontró «… pruebas suficientes para recomendar las pruebas para la variante genética 9p21 u otras 57 variantes en 28 genes para evaluar el riesgo de enfermedad cardiovascular (ECV ) en la población general, específicamente cardiopatía y accidente cerebrovascular. El EWG encontró que la magnitud del beneficio neto de la salud del uso de cualquiera de las pruebas solas o en combinación es insignificante. El EWG desalienta el uso clínico y lo identifica como menos que una prueba más compatible con mejores resultados clínicos. En base a la evidencia disponible, el grado de certidumbre global del beneficio neto de la salud se considera «bajo» «63.
Recomendaciones de EE.UU. Preventive Services Task ForceNo hay recomendaciones del Services Task Force de Estados Unidos para genotipado de 9p21 para identificar el riesgo de las enfermedades cardio-vasculares.
Cobertura Nacional de MedicareNo hay una determinación de cobertura nacional (NCD). En ausencia de una de las ENT, las decisiones de cobertura se dejan a la discreción de las compañías locales de Medicare.

Genetic testing for hereditary pancreatitis may be considered medically necessary for patients aged 18 years and younger with unexplained acute recurrent (>1 episode) or chronic pancreatitis with documented elevated amylase or lipase levels.

Genetic testing for hereditary pancreatitis is considered investigational in all other situations.

Chronic Myelogenous Leukemia

BCR-ABL1 qualitative testing for the presence of the fusion gene may be considered medically necessary for the diagnosis of chronic myeloid leukemia (see Policy Guidelines section).

BCR-ABL1 testing for messenger RNA transcript levels by quantitative real-time reverse transcription-polymerase chain reaction at baseline before initiation of treatment and at appropriate intervals (see Policy Guidelines section) may be considered medically necessary for monitoring of chronic myeloid leukemia treatment response and remission.

Evaluation of ABL kinase domain (KD) single nucleotide variants to assess individuals for tyrosine kinase inhibitor resistance may be considered medically necessary when there is an inadequate initial response to treatment or any sign of loss of response (see Policy Guidelines section); and/or when there is a progression of the disease to the accelerated or blast phase.

Evaluation of ABL KD single nucleotide variants is considered investigational for monitoring in advance of signs of treatment failure or disease progression.

Acute Lymphoblastic Leukemia

BCR-ABL1 testing for messenger RNA transcript levels by quantitative real-time reverse transcription-polymerase chain reaction at baseline before initiation of treatment and at appropriate intervals during therapy (see Policy Guidelines section) may be considered medically necessary for monitoring of Philadelphia chromosome-positive acute lymphoblastic leukemia treatment response and remission.

Evaluation of ABL KD single nucleotide variants to assess individuals for tyrosine kinase inhibitor resistance may be considered medically necessary when there is an inadequate initial response to treatment or any sign of loss of response.

Evaluation of ABL KD single nucleotide variants is considered investigational for monitoring in advance of signs of treatment failure or disease progression.

General genetic cancer susceptibility panel testing is considered investigational; however, when the coverage criteria of other policies is met (see related policies), then limited genetic cancer susceptibility panels including only the gene variants for which a given member qualifies may be considered medically necessary.

Genetic testing for DMD gene variants may be considered medically necessary under the following conditions:

In a male with signs and symptoms of a dystrophinopathy in order to confirm the diagnosis and direct treatment.

For at-risk female relatives (see Policy Guidelines and Benefit Application sections):

To confirm or exclude the need for cardiac surveillance.

For preconception testing to determine the likelihood of an affected offspring in a woman considering a pregnancy.

For at-risk male offspring (see Policy Guidelines and Benefit Application sections):

To confirm or exclude the need for medical and cardiac surveillance.

Genetic testing for DMD gene variants is considered investigational in all other situations.

Genotyping to determine cytochrome P450 2C9 (CYP2C9), P450 4F2 (CYP4F2), and vitamin K epoxide reductase subunit C1 (VKORC1) genetic variants is considered investigational for the purpose of managing the administration and dosing of warfarin, including use in guiding the initial warfarin dose to decrease time to stable INR and to reduce the risk of serious bleeding.

Methylation analysis of the O6-­methylguanine DNA methyltransferase (MGMT) gene promoter from glioma tumor tissue is medically necessary for individuals who meet the following criteria:

They have a tumor type consistent with high-­grade malignant glioma (eg, glioblastoma multiforme, anaplastic astrocytoma); and
Candidate for temozolomide therapy or radiotherapy; and
Methylation results will be used to direct their therapy choices.

MGMT promoter methylation analysis is investigational in situations that do not meet the above criteria.

Preimplantation genetic diagnosis may be considered medically necessary as an adjunct to in vitro fertilization (IVF) in couples not known to be infertile who meet one of the criteria listed below.

For evaluation of an embryo at an identified elevated risk of a genetic disorder such as when:

Both partners are known carriers of a single-gene autosomal recessive disorder
One partner is a known carrier of a single-gene autosomal recessive disorder, and the partners have an offspring who has been diagnosed with that recessive disorder
One partner is a known carrier of a single-gene autosomal dominant disorder
One partner is a known carrier of a single X-linked disorder, or

For evaluation of an embryo at an identified elevated risk of structural chromosomal abnormality such as for a:

Parent with balanced or unbalanced chromosomal translocation.

Preimplantation genetic diagnosis as an adjunct to IVF is considered investigational in patients or couples who are undergoing IVF in all situations other than those specified above.

Preimplantation genetic screening as an adjunct to IVF is considered investigational in patients or couples who are undergoing IVF in all situations.

Individual genetic testing for the diagnosis of Marfan syndrome, Ehlers-Danlos syndrome type IV, other syndromes associated with thoracic aortic aneurysms and dissections, and related disorders, and panels comprised entirely of focused genetic testing limited to the following genes: FBN1 and MYH11; ACTA2, TGFBR1, and TGFBR2; and COL3A1 may be considered medically necessary when signs and symptoms of a connective tissue disorder are present, but a definitive diagnosis cannot be made using established clinical diagnostic criteria.

Individual, targeted familial variant testing for Marfan syndrome, Ehlers-Danlos syndrome type IV, other syndromes associated with thoracic aortic aneurysms and dissections, and related disorders, for assessing future risk of disease in an asymptomatic individual, may be considered medically necessary when there is a known pathogenic variant in the family.

Genetic testing panels for Marfan syndrome, Ehlers-Danlos syndrome type IV, other syndromes associated with thoracic aortic aneurysms and dissections, and related disorders that are not limited to focused genetic testing are considered investigational.

Evaluation of biomarker genes is considered investigational for detection of lymph node metastases in patients with breast cáncer.

One time genotypic or phenotypic analysis of thiopurine methyltransferase (TPMT) and nudix hydrolase (NUDT15) may be considered medically necessary in patients beginning therapy with azathioprine, mercaptopurine, or thioguanine OR in individuals on thiopurine therapy with abnormal complete blood count results that do not respond to dose reduction.

Genotypic and/or phenotypic analysis of the TPMT and NUDT15 genes is considered investigational in all other situations.

Analysis of the metabolite markers of azathioprine and mercaptopurine, including 6-methyl-mercaptopurine ribonucleotides and 6-thioguanine nucleotides, is considered investigational.

Targeted genetic testing for a known familial variant in the presenilin (PSEN) genes or amyloid-beta precursor protein (APP) gene associated with autosomal dominant early-onset Alzheimer disease may be considered medically necessary in an asymptomatic individual to determine future risk of disease when the following criteria are met:

The individual has a close relative (ie, first- or second-degree relative) with a known familial variant associated with autosomal dominant early-onset Alzheimer disease (see Policy Guidelines) AND

Results of testing will inform reproductive decision making.

Genetic testing for variants in presenilin (PSEN) genes or amyloid-beta precursor protein (APP) gene associated with autosomal dominant early-onset Alzheimer disease may be considered medically necessary in an asymptomatic individual to determine future risk of disease when the following criteria are met:

The individual has a family history of dementia consistent with autosomal dominant Alzheimer disease for whom the genetic status of the affected family members is unavailable AND

Results of testing will inform reproductive decision making.

Genetic testing for the risk assessment of Alzheimer disease in asymptomatic individuals is considered investigational in all other situations. Genetic testing includes but is not limited to, testing for the apolipoprotein E (APOE) epsilon 4 allele or triggering receptor expressed on myeloid cells 2 (TREM2).

Genetic testing to guide initiation or management of a U.S. Food and Drug Administration-approved amyloid-beta targeting therapy (eg, aducanumab) is considered investigational. Genetic testing includes but is not limited to, testing for the APOE epsilon 4 allele.

Gene expression profiling is considered investigational to evaluate the site of origin of a tumor of unknown primary, or to distinguish a primary from a metastatic tumor.

Targeted Risk-Based Carrier Screening

Targeted carrier screening for X-linked and autosomal recessive genetic diseases is considered medically necessary for individuals who are pregnant or are considering pregnancy and are at increased risk of having offspring with an X-linked or autosomal recessive disease when one of the following criteria is met:

One or both individuals have a first- or second-degree relative who is affected; OR

One individual is known to be a carrier; OR

One or both individuals are members of a population known to have a carrier rate that exceeds a threshold considered appropriate for testing for a particular condition.

AND all of the following criteria are met:

The natural history of the disease is well understood and there is a reasonable likelihood that the disease is one with high morbidity or early mortality in the homozygous or compound heterozygous state (see Policy Guidelines);

Alternative biochemical or other clinical tests to definitively diagnose carrier status are not available, or, if available, provide an indeterminate result or are individually less efficacious than genetic testing;

The genetic test has adequate clinical validity to guide clinical decision-making and residual risk is understood;

An association of the marker with the disorder has been established;

If targeted testing is performed by a panel, the panel meets the minimum number of recommended gene variants but does not exceed the maximum, as determined by professional clinical guidelines (see Policy Guidelines). Non-targeted panels can be used instead of targeted testing when the criteria for non-targeted carrier screening are met (see below);

Previous carrier screening or individual targeted gene testing for the gene variant(s) of interest has not been performed (see Policy Guidelines).

All targeted carrier screening not meeting any of the above criteria is considered investigational.

First-degree relatives include a biological parent, brother, sister, or child; second-degree relatives include a biologic grandparent, aunt, uncle, niece, nephew, grandchildren, and half-sibling.

Non-Targeted Carrier Screening

Non-targeted carrier screening panels for autosomal recessive and X-linked genetic disorders may be considered medically necessary as an alternative to testing of individual genes (eg, SMN1 gene and CFTR gene) for individuals who are pregnant or are considering pregnancy at any risk level including high risk and average risk when all of the following criteria are met:

The natural history of each disease is well understood and there is reasonable likelihood that the disease is one with high morbidity or early mortality in the homozygous or compound homozygous state (see Policy Guidelines);

Alternative biochemical or other clinical tests to definitively diagnose carrier status are not available, or, if available, provide an indeterminate result or are individually less efficacious than genetic testing;

The genetic test has adequate clinical validity to guide clinical decision-making and residual risk is understood;

An association of the markers with the disorders has been established;

If testing is performed by a panel, the panel meets the minimum number of recommended gene variants but does not exceed the maximum, as determined by professional clinical guidelines (see Policy Guidelines);

Previous carrier screening has not been performed (see Policy Guidelines).

Non-targeted carrier screening panels are considered investigational in all other situations when above criteria are not met (see Policy Guidelines).

Genetic testing for diagnosis and management of mental health disorders is considered investigational in all situations, including but not limited to the following:

To confirm a diagnosis of a mental health disorder in an individual with symptoms.

To predict future risk of a mental health disorder in an asymptomatic individual.

To inform the selection or dose of medications used to treat mental health disorders, including but not limited to the following medications:

selective serotonin reuptake inhibitors

selective norepinephrine reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors

tricyclic antidepressants

antipsychotic drugs.

Genetic testing panels for mental health disorders, including but not limited to the Genecept Assay, STA2R test, the GeneSight Psychotropic panel, the Proove Opioid Risk assay, and the Mental Health DNA Insight panel, are considered investigational for all indications.

Genetic testing for genes associated with infantile- and early-childhood onset epilepsy syndromes in individuals with infantile- and early-childhood-onset epilepsy syndromes in which epilepsy is the core clinical symptom (see Policy Guidelines section) may be considered medically necessary if positive test results may:

Lead to changes in medication management; AND/OR

Lead to changes in diagnostic testing such that alternative potentially invasive tests are avoided; AND/OR

Lead to changes in reproductive decision making.

Genetic testing for epilepsy is considered investigational for all other situations.

Use of gene expression analysis and protein biomarkers to guide management of prostate cancer is considered investigational in all situations.

For individuals who have thyroid nodules without strong clinical or radiologic findings suggestive of malignancy in whom surgical decision making would be affected by test results, the use of either of the following types of molecular marker testing or gene variant analysis in fine needle aspirates of thyroid nodules with indeterminate cytologic findings (ie, Bethesda diagnostic category III [atypia/follicular lesion of undetermined significance] or Bethesda diagnostic category IV [follicular neoplasm/suspicion for a follicular neoplasm]) may be considered medically necessary:

Afirma® Genomic Sequencing Classifier; or

ThyroSeq®.

The use of any of the following types of molecular marker testing or gene variant analysis in fine needle aspirates of thyroid nodules with indeterminate findings (Bethesda diagnostic category III [atypia/follicular lesion of undetermined significance] or Bethesda diagnostic category IV [follicular neoplasm/suspicion for a follicular neoplasm]) or suspicious findings (Bethesda diagnostic category V [suspicious for malignancy]) to rule in malignancy to guide surgical planning for initial resection rather than a 2-stage surgical biopsy followed by definitive surgery may be considered medically necessary:

ThyroSeq;

ThyraMIR® microRNA/ThyGenX®;

Afirma BRAF after Afirma Genomic Sequencing Classifier; or

Afirma MTC after Afirma Genomic Sequencing Classifier.

Gene expression classifiers, genetic variant analysis, and molecular marker testing in fine needle aspirates of the thyroid not meeting criteria outlined above, including but not limited to use of RosettaGX Reveal and single-gene TERT testing, are considered investigational.

Standard whole exome sequencing, with trio testing when possible (see Policy Guidelines), may be considered medically necessary for the evaluation of unexplained congenital or neurodevelopmental disorders in children when ALL of the following criteria are met:

Documentation that the individual has been evaluated by a clinician with expertise in clinical genetics, including at minimum a family history and phenotype description, and counseled about the potential risks of genetic testing.

There is potential for a change in management and clinical outcome for the individual being tested.

A genetic etiology is considered the most likely explanation for the phenotype despite previous genetic testing (eg, chromosomal microarray analysis and/or targeted single-gene testing), OR when previous genetic testing has failed to yield a diagnosis, and the affected individual is faced with invasive procedures or testing as the next diagnostic step (eg, muscle biopsy).

Rapid whole exome sequencing or rapid whole genome sequencing, with trio testing when possible (see Policy Guidelines), may be considered medically necessary for the evaluation of critically ill infants in neonatal or pediatric intensive care with a suspected genetic disorder of unknown etiology when BOTH of the following criteria are met:

At least one of the following criteria is met:

Multiple congenital anomalies (see Policy Guidelines);

An abnormal laboratory test or clinical features suggests a genetic disease or complex metabolic phenotype (see Policy Guidelines);

An abnormal response to standard therapy for a major underlying condition.

None of the following criteria apply regarding the reason for admission to intensive care:

An infection with normal response to therapy;

Isolated prematurity;

Isolated unconjugated hyperbilirubinemia;

Hypoxic Ischemic Encephalopathy;

Confirmed genetic diagnosis explains illness;

Isolated Transient Neonatal Tachypnea; or

Nonviable neonates.

Whole exome sequencing is considered investigational for the diagnosis of genetic disorders in all other situations.

Repeat whole exome sequencing for the diagnosis of genetic disorders, including re-analysis of previous test results, is considered investigational.

Whole genome sequencing is considered investigational for the diagnosis of genetic disorders in all other situations.

Whole exome sequencing and whole genome sequencing are considered investigational for screening for genetic disorders.

Genetic testing to confirm a diagnosis of α-thalassemia is considered investigational.

Genetic testing of individuals with hemoglobin H disease (α-thalassemia intermedia) to determine prognosis is considered investigational.

Preconception (carrier) testing for α-thalassemia in prospective parents may be considered medically necessary when both parents have evidence of possible α-thalassemia (including α-thalassemia minor, hemoglobin H disease [α-thalassemia intermedia], or α-thalassemia minima [silent carrier] ) based on biochemical testing (see Policy Guidelines section).

Genetic testing for α-thalassemia in other clinical situations (recognizing that prenatal testing is not addressed in this policy) is considered investigational.