Coverage Policy Manual
Policy #: 2000002
Category: Radiology
Initiated: December 1999
Last Review: December 2023
  PET or PET/CT for Non-Hodgkins Lymphoma and Leukemia
Description:
Note:  This policy is intended for those members with contracts that do not have requirements for prior approval for imaging procedures through an independent imaging review organization.
 
 “PET scan” refers to FDG PET or PET/CT.
 
Positron Emission Tomography (PET) imaging uses radiotracers that can reveal both anatomical and physiological information.  The glucose analog, 2-[fluorine-18]-Fluoro-2-deoxy-D-glucose (FDG) is useful in cancer imaging because it has been found that tumor cells show increased utilization of glucose compared to non-malignant tissue and is the most common radiotracer that is utilized. For certain malignancies PET scans have been shown to be more accurate than other non-invasive tests in detecting malignant disease.  However, as with all diagnostic tests, PET scans do not detect cancer 100% of the time that cancer is present (a false negative test), nor do all positive PET scans represent the presence of malignant disease (a false positive test).  A false negative test may occur because a critical volume of malignant cells is necessary for a PET scan to be positive. PET scans may be false positive in the presence of inflammation or granulomatous disease.
 
Definitions
 
Screening – testing in the absence of an established or clinically suspected diagnosis
 
Diagnosis - testing based on a reasonable clinical suspicion of a particular condition or disorder
 
Diagnostic Workup – initial staging of documented malignancy
 
Management – testing to direct therapy of an established condition, which may include preoperative or postoperative imaging, or imaging performed to evaluate the response to nonsurgical intervention. In oncologic imaging, management applies to patients with measurable disease and to imaging performed before or after planned treatment intervention, therapy response, restaging or clinically suspected recurrence.
 
Surveillance – periodic assessment following completion of therapy. In oncologic imaging, surveillance applies to asymptomatic patients in remission and/or without measurable disease
 
Cannot be performed or is nondiagnostic – applies when the test:
    • Is positive or indeterminate for clinically significant pathology when the information provided about the abnormality by the test is not sufficient to direct subsequent management
    • Is negative when the negative likelihood ratio of the test is both insufficient to confidently exclude the absence of suspected disease and unable to direct subsequent management. This typically applies in scenarios with moderate to high clinical pretest probability with negative testing or low pretest probability with clear evidence for net benefit
    • Has been previously nondiagnostic because of a persistent clinical factor (e.g., body habitus, immobility) that is very likely to make retesting nondiagnostic as well Cannot be performed due to a medical contraindication (e.g., contrast nephrotoxicity, allergy, or in highly radiation sensitive populations such as pediatrics and pregnancy) or reasonable unavailability related to lack of local expertise or service availability
Standard or conventional imaging: Refers to imaging that does not require a PET/CT. Depending on the clinical scenario and individual patient circumstances, this may include computed tomography, magnetic resonance imaging, ultrasound and/or scintigraphy.
  
Policy/
Coverage:
EFFECTIVE MARCH 14, 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
FDG-PET/CT for patients with Acute Leukemia, Chronic lymphocytic leukemia/small lymphocytic lymphoma, and Non-Hodgkin lymphomas meets member benefit certificate primary coverage criteria for effectiveness for improving health outcomes and is covered for:
 
Acute Leukemia
Diagnostic Workup:
Indicated in EITHER of the following scenarios:
        • Clinical suspicion for extramedullary disease or lymphadenopathy
        • When standard imaging cannot be performed or is nondiagnostic
Management:
Indicated in ANY of the following scenarios:
        • Relapsed or refractory extramedullary disease
        • Treatment response of acute lymphoblastic leukemia (ALL) with lymphomatous extramedullary disease
        • When standard imaging cannot be performed or is nondiagnostic
Chronic lymphocytic leukemia or small lymphocytic lymphoma
Diagnostic Workup:
Indicated for suspicion of Richter’s transformation when PET is utilized to direct biopsy
 
Management:
Indicated for suspicion of Richter’s transformation when PET is utilized to direct biopsy
Lymphoma – Non-Hodgkin: Indolent non-Hodgkin lymphoma
Diagnostic Workup:
Indicated in ANY of the following scenarios:
        • Initial evaluation of suspected lymphoma when lymph nodes are not amenable to biopsy
        • Evaluation of suspected transformation to a more aggressive lymphoma based on clinical signs or symptoms
        • Prior to initiation of therapy
Management:
Indicated in ANY of the following scenarios:
        • Radiation planning prior to definitive or consolidative treatment for indolent, aggressive, and highly aggressive non-Hodgkin’s lymphoma
        • Post-treatment response evaluation, when initial PET scan has demonstrated FDG uptake
        • Evaluation of suspected recurrence or progression of disease based on standard imaging when there is an indication to resume systemic treatment
        • Evaluation of suspected transformation to a more aggressive lymphoma based on clinical signs or symptoms
Lymphoma – Non-Hodgkin: Intermediate and High grade non-Hodgkin lymphoma
(Includes Castleman Disease, Post-Transplant Lymphoproliferative Disorders)
Diagnostic Workup:
Indicated in EITHER of the following scenarios:
            • Initial evaluation of suspected lymphoma when lymph nodes are not amenable to biopsy
            • Initial staging (often used as an adjunct to CT chest/abdomen/pelvis)
Management:
Indicated in ANY of the following scenarios:
            • Radiation planning prior to definitive or consolidative treatment for indolent, aggressive, and highly-aggressive non-Hodgkin’s lymphoma
            • Interim restaging following 2-4 cycles of treatment for stage III and IV disease
            • Evaluation at completion of therapy
            • Evaluation of suspected recurrence or progression of disease based on standard imaging or objective signs/symptoms
 
For fully-insured contracts subject to Act 583 of Arkansas legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET/CT for patients with for patients with Acute Leukemia, Chronic lymphocytic leukemia/small lymphocytic lymphoma, and Non-Hodgkin lymphomas is does not meet member benefit certificate primary coverage criteria of effectiveness for improving health outcomes and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
For members with contracts without primary coverage criteria, PET/CT for patients with for patients with Acute Leukemia, Chronic lymphocytic leukemia/small lymphocytic lymphoma, and Non-Hodgkin lymphomas is considered investigational and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
*For fully-insured contracts subject to Act 583 of Arkansas legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Note: Standard or conventional imaging: Refers to imaging that does not require a PET/CT. Depending on the clinical scenario and individual patient circumstances, this may include computed tomography, magnetic resonance imaging, ultrasound and/or scintigraphy.
 
EFFECTIVE MARCH 13, 2022 - April 14, 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
For all fully insured contracts, all self-funded church-sponsored health plans and all self-funded government-sponsored health plans other than the Arkansas State and Public School Employees program, the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
FDG-PET/CT for patients with Acute Leukemia, Chronic lymphocytic leukemia/small lymphocytic lymphoma, and Non-Hodgkin lymphomas meets member benefit certificate primary coverage criteria for effectiveness for improving health outcomes and is covered for:
 
Acute Leukemia
 
Diagnostic Workup:
Indicated in EITHER of the following scenarios:
        • Clinical suspicion for extramedullary disease or lymphadenopathy
        • When standard imaging cannot be performed or is nondiagnostic
Management:
Indicated in ANY of the following scenarios:
        • Relapsed or refractory extramedullary disease
        • Treatment response of acute lymphoblastic leukemia (ALL) with lymphomatous extramedullary disease
        • When standard imaging cannot be performed or is nondiagnostic
 
Chronic lymphocytic leukemia or small lymphocytic lymphoma
 
Diagnostic Workup:
Indicated for suspicion of Richter’s transformation when PET is utilized to direct biopsy
 
Management:
Indicated for suspicion of Richter’s transformation when PET is utilized to direct biopsy
 
Lymphoma – Non-Hodgkin: Indolent non-Hodgkin lymphoma
 
Diagnostic Workup:
Indicated in ANY of the following scenarios:
        • Initial evaluation of suspected lymphoma when lymph nodes are not amenable to biopsy
        • Evaluation of suspected transformation to a more aggressive lymphoma based on clinical signs or symptoms
        • Prior to initiation of therapy
Management:
Indicated in ANY of the following scenarios:
        • Radiation planning prior to definitive or consolidative treatment for indolent, aggressive, and highly aggressive non-Hodgkin’s lymphoma
        • Post-treatment response evaluation, when initial PET scan has demonstrated FDG uptake
        • Evaluation of suspected recurrence or progression of disease based on standard imaging when there is an indication to resume systemic treatment
        • Evaluation of suspected transformation to a more aggressive lymphoma based on clinical signs or symptoms
 
Lymphoma – Non-Hodgkin: Intermediate and High grade non-Hodgkin lymphoma
(Includes Castleman Disease, Post-Transplant Lymphoproliferative Disorders)
 
Diagnostic Workup:
Indicated in EITHER of the following scenarios:
        • Initial evaluation of suspected lymphoma when lymph nodes are not amenable to biopsy
        • Initial staging (often used as an adjunct to CT chest/abdomen/pelvis)
Management:
Indicated in ANY of the following scenarios:
        • Radiation planning prior to definitive or consolidative treatment for indolent, aggressive, and highly-aggressive non-Hodgkin’s lymphoma
        • Evaluation of response following 2 to 4 cycles of treatment for stage III and IV disease
        • Post-treatment evaluation
        • Evaluation of suspected recurrence or progression of disease based on standard imaging or objective signs/symptoms
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET/CT for patients with for patients with Acute Leukemia, Chronic lymphocytic leukemia/small lymphocytic lymphoma, and Non-Hodgkin lymphomas is does not meet member benefit certificate primary coverage criteria of effectiveness for improving health outcomes and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
 
For members with contracts without primary coverage criteria, PET/CT for patients with for patients with Acute Leukemia, Chronic lymphocytic leukemia/small lymphocytic lymphoma, and Non-Hodgkin lymphomas is considered investigational and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
*For all fully insured contracts, all self-funded church-sponsored health plans and all self-funded government-sponsored health plans other than the Arkansas State and Public School Employees program, the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Note: Standard or conventional imaging: Refers to imaging that does not require a PET/CT. Depending on the clinical scenario and individual patient circumstances, this may include computed tomography, magnetic resonance imaging, ultrasound and/or scintigraphy.
 
 
Effective Prior to MARCH 13, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
FDG-PET/CT for patients with Non-Hodgkin Lymphoma meets member benefit certificate primary coverage criteria for effectiveness for improving health outcomes for:
 
NON-HODGKIN: CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LYMPHOMA
 
Diagnostic Workup
As clinically indicated for suspicion of Richter’s transformation when PET is utilized to direct biopsy
 
Management
As clinically indicated for suspicion of Richter’s transformation when PET is utilized to direct biopsy
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
NON-HODGKIN: INDOLENT NON-HODGKIN LYMPHOMA
 
Diagnostic Workup
Indicated in ANY of the following:  
    • Initial evaluation of suspected lymphoma when lymph nodes are not amenable to biopsy; or
    • Evaluation of suspected transformation to a more aggressive lymphoma based on clinical signs or symptoms; or
    • Prior to initiation of therapy.
 
Management
As clinically indicated in ANY of the following:
    • Radiation planning prior to definitive or consolidative treatment for indolent, aggressive, and highly aggressive non-Hodgkin’s lymphoma; or
    • Post-treatment response evaluation, when initial PET scan has demonstrated FDG uptake; or
    • Evaluation of suspected recurrence or progression of disease based on standard imaging when there is an indication to resume systemic treatment; or
    • Evaluation of suspected transformation to a more aggressive lymphoma based on clinical signs or symptoms.
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
NON-HODGKIN: INTERMEDIATE AND HIGH-GRADE NON-HODGKIN LYMPHOMA
 
Diagnostic Workup
Indicated in EITHER of the following:
    • Initial evaluation of suspected lymphoma when lymph nodes are not amenable to biopsy; OR  
    • Initial staging (often used as an adjunct to CT chest/abdomen/pelvis).
 
Management
Indicated in ANY of the following:
    • Radiation planning prior to definitive or consolidative treatment for indolent, aggressive and highly-aggressive non-Hodgkin’s lymphoma; or
    • Evaluation of response following 2 to 4 cycles of treatment for stage III and stage IV disease; or
    • Post-treatment evaluation; or
    • Evaluation of suspected recurrence or progression of disease based on standard imaging or objective signs/symptoms.
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET/CT for patients with Non-Hodgkin Lymphoma does not meet member benefit certificate primary coverage criteria of effectiveness for improving health outcomes for:
    • Screening and surveillance;
    • Any other indication not specifically listed as covered above.
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
For members with contracts without primary coverage criteria, PET scan for patients with Non-Hodgkin Lymphoma is considered investigational for:  
    • Screening and surveillance;
    • Any other indication not specifically listed as covered above.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to May 2021
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET scan imaging meets member benefit certificate primary coverage criteria for effectiveness and is covered in members with contracts without primary coverage criteria for patients with non-Hodgkin’s lymphoma who are undergoing initial staging of their disease.
 
PET scan imaging meets member benefit certificate primary coverage criteria for effectiveness and is covered in members with contracts without primary coverage criteria for patients with non-Hodgkin’s lymphoma for restaging of disease 3 – 12 weeks after completion of therapy, or for patients who have evidence of recurrence of disease (e.g., clinical, laboratory, or radiological)
  
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET scan imaging does not meet member benefit certificate primary coverage criteria for effectiveness for patients with non-Hodgkin’s lymphoma for monitoring after 1-4 cycles of chemotherapy or chemoimmunotherapy to determine prognosis or to recommend change in therapy because this use is recommended against by NCCN, and is under study in ongoing clinical trials (NCT01285765; NCT00530179; NCT01359592; NCT01410630; NCT00544219; NCT00286832; NCT00712582; NCT00754117).
 
PET scan imaging does not meet member benefit certificate primary coverage criteria for effectiveness for patients with non-Hodgkin’s lymphoma  for surveillance because there is a lack of studies that indicate this testing improves health outcomes, and there is a conflict amongst experts regarding the effectiveness of this testing.
 
PET scan imaging for diagnosis does not meet member benefit certificate primary coverage criteria for effectiveness as this use is specifically recommended against by major medical publications and national medical groups.
 
For those contracts without Primary Coverage Criteria, PET scanning is considered investigational:  
    • to monitor response to chemotherapy, or chemoimmunotherapy to determine prognosis or to recommend change in therapy because this use is recommended against by NCCN, and is under study in ongoing clinical trials  
    • for surveillance because there is a lack of studies that indicate this testing improves health outcomes, and there is a conflict amongst experts regarding the effectiveness of this testing.
    • for diagnosis as this use is specifically recommended against by major medical publications and national medical groups.  
Investigational services are specific contract exclusions in most member benefit certificates of coverage.   
 
NOTE: PET scanning should not be done for imaging of tumors that are known not to be FDG-avid.
  
NOTE: The decision to give salvage therapy, after PET has been used to distinguish between viable tumors and necrosis or fibrosis in residual masses after treatment, should be made only after positive PET findings have been confirmed by biopsy.  (Juweid ME, Cheson BD. NEJM, 2006;354:496-507)
Rationale:
PET has been investigated for Diagnosis, Initial staging, Restaging, Monitoring, and Surveillance of non-Hodgkin’s lymphoma.  
 
PET scanning is not recommended for diagnosis because the positive predictive value and negative predictive value are inferior to tissue sampling for diagnosis.  
 
The sensitivity and specificity of PET are superior to other imaging methods, however, for initial staging, in that PET scanning has been found to detect an additional number or lymphoma manifestations which results in a modification of disease in about 15% to 20% of patients and impact on management in 5%-15% (Moog, 1997; Moog, 2008; Buchmann, 2001).  
 
PET for restaging at therapy conclusion, typically performed within 3-12 weeks of completing treatment, is currently the most routinely utilized application of restaging PET, and is clearly supported by the large body of evidence showing a high negative predictive value.  PET may not, however, detect microscopic disease (Schaefer, 2004; Juweid, 2007; Chesson, 2007; Juweid, 2008).  
 
PET for surveillance in non-Hodgkin’s lymphoma has been controversial.  Zinzani, et al reported an extensive study on surveillance in 421 patients with NHL and Hodgkin’s Lymphoma, and the percent detection of proven relapse was higher than CT or clinical assessment.  It did not, however, determine if surveillance was cost-effective or whether the scanning results in meaningful changes in patient management or outcome (Zinzani, 2009).  Jerusalem (2003) and Chesson (2009) state that PET for surveillance cannot be recommended outside a clinical trial.  NCCN also does not recommend surveillance.  
 
Most early studies of PET for monitoring appear to have been performed because of the prognostic information provided, with no indication that the results of these scans were actually used to alter treatment (Jerusalem, 2000; Mikhaeel, 2000; Spaepen, 2001; Kostakoglu, 2002; Lin, 2007; Weber, 2007; Itti, 2009; Dupuis, 2009).  The conclusion of most is that the power of a negative interim FDG-PET scan after 1-4 cycles of chemoimmunotherapy confers excellent prognosis in patients with diffuse large B-cell lymphoma.  At the same time, at least one recent study (Pregno, 2012) found that positive interim PET is not predictive of a worse outcome in DLBCL; a review of PET for FDG-PET in patients with lymphoma concludes that this use of PET imaging should be reserved for restaging curable lymphomas, sparing other patients expense and radiation exposure until clinical trials validate the role of this technology in other settings (Cheson, 2009).  NCCN Guidelines, Version 2.2012 states that “interim PET scan is not recommended outside the setting of a clinical trial, and is not recommended to be used to guide changes in therapy.
 
2014 Update
 
A literature search conducted through April 2014 did not reveal any new information that would prompt a change in the coverage statement.
 
The NCCN guidelines for non-Hodgkin lymphoma and Hodgkin lymphoma indicate PET-CT may be used in staging, restaging, and evaluating treatment response (NCCN, 2014).
  
2015 Update
 
A literature search conducted through January 2015 did not reveal any new information that would prompt a change in the coverage statement.
 
2018 Update
 Annual policy review completed with a literature search using the MEDLINE database through February 2018. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Lymphoma Restaging
A systematic review and meta-analysis by Adams and Kwee evaluated the proportion of false positive lesions at interim and end-of-treatment as detected by 18F-FDG-PET in patients with lymphoma (Adams, 2016). The literature search, conducted through January 2016, identified 11 studies (total N=139 patients) for inclusion. Study quality was moderate, as assessed by the QUADAS-2 tool. The weighted summary proportion of false-positive results among all biopsied lesions both during and after completion of treatment was 56% (95% CI, 33% to 77%). Subgroup analyses found the following 18F-FDG-PET false positive proportions for: interim non-Hodgkin lymphoma (83%; 95% CI, 72% to 90%); end-of-treatment non-Hodgkin lymphoma (31%; 95% CI, 4% to 84%), and end-of-treatment Hodgkin lymphoma (23%; 95%
CI, 5% to 65%). We found no studies calculating the false-positive rate for interim Hodgkin lymphoma.
 
A 2015 systematic review by Adams et al focused for the outcomes of patients with Hodgkin lymphoma who had negative residual mass after treatment with 18F-FDG-PET(Adams, 2015). When a persistent mass is non-FDG-avid, the patient is considered to be in complete remission, though the significance of having a residual mass is unclear. The literature search, conducted through December 2014, identified 5 studies (total N=727 patients) for inclusion. Follow-up of patients in the studies ranged from 1 to 13 years. The pooled relapse proportion was 6.8% (95% CI, 2.6% to 12.5%).
 
Lymphoma Management
A 2017 systematic review by Adams and Kwee evaluated the prognostic value of 18F-FDG-PET in
patients with refractory or relapsed Hodgkin lymphoma considering autologous cell transplantation (Adams, 2017). The literature search, conducted through May 2016, identified 11 studies (total N=664 patients) for inclusion. In general, the overall quality of selected studies was poor, based on Quality in Prognosis Studies (QUIPS). Pooled sensitivity and specificity of pretransplant 18F-FDG-PET in predicting treatment failure were 54% (95% CI, 44% to 63%) and 73% (95% CI, 67% to 79%), respectively. Pooled sensitivity and specificity of pretransplant 18F-FDG-PET in predicting death after treatment were 55% (95% CI, 39% to 70%) and 69% (95% CI, 61% to 76%), respectively.
 
A 2016 meta-analysis by Adams and Kwee evaluated the prognostic value of 18F-FDG-PET in patients
with aggressive non-Hodgkin lymphoma considering autologous cell transplantation (Adams, 2016). The literature search, conducted through July 2015, identified 11 studies (total N=745 patients) for inclusion. The overall quality of selected studies was moderate, based on QUIPS criteria. Patients with positive pretransplant 18F-FDG-PET results had progression-free survival (PFS) rates ranging from 0% to 52%. Patients with negative pretransplant 18F-FDG-PET results had PFS rates ranging from 55% to 85%. OS was 17% to 77% in patients with positive 18F-FDG-PET results and 78% to 100% in patients with negative 18F-FDGPET results. Based on 5 studies, pooled sensitivity and specificity of pretransplant 18F-FDG-PET predicting treatment failure (defined as progressive, residual, or relapsed disease) were 67% (95% CI, 58% to 75%) and 71% (95% CI, 64% to 77%), respectively.
 
A 2015 systematic review by Zhu et al evaluated the prognostic value of 18F-FDG-PET in patients with
diffuse B-cell lymphoma treated with rituximab-based immune chemotherapy (Zhu, 2015). The literature search identified 11 studies (N=1081) for inclusion. The pooled hazard ratio comparing PFS of patients with positive interim 18F-FDG-PET results and negative interim 18F-FDG-PET results was 3.0 (95% CI, 2.3 to 3.9). Patients with a negative interim 18F-FDG-PET result had a higher complete remission rate than patients with a positive interim 18F-FDG-PET result (relative risk, 5.5; 95% CI, 2.6 to 11.8).
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2019. No new literature was identified that would prompt a change in the coverage statement.
 
2020 Update
A literature search was conducted through February 2020.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2021. No new literature was identified that would prompt a change in the coverage statement.
 
December 2021 Update
A literature review was performed through September 2021. Following is a summary of the key literature to date.
 
Acute leukemias include acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and acute promyelocytic leukemia (APL).
 
DIAGNOSTIC WORKUP
Lymphoma is staged using the Lugano classification system. For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), CT chest, abdomen, and pelvis is not routinely indicated unless clinically indicated. (3) PET/CT is most accurate for staging and interim assessment of lymphomas with high FDG avidity like diffuse large B-cell lymphoma, follicular NHL, and nodal marginal zone lymphoma, but may be less accurate for CLL/SLL, marginal zone lymphoma, and hairy cell leukemia. (4, 5)
 
For staging of indolent NHL, the evidence comparing the accuracy of PET/CT to CT alone is mixed. In a recent prospective trial, both modalities performed equally well at initial staging for both indolent and intermediate grade lymphomas.6 However, multiple retrospective trials have found significantly higher sensitivity for PET/CT (94%-98%) and a resultant change of management based on PET findings in 34% of patients. (7, 8)
 
For aggressive and highly aggressive NHL, a PET/CT with or without CT chest, abdomen and pelvis with contrast is indicated. In a retrospective study comparing CT to PET for Hodgkin lymphoma and high-grade NHL, the sensitivity of PET/CT versus contrast-enhanced CT was 94% vs. 88% respectively. For evaluation of organ involvement, sensitivity of PET/CT versus contrast-enhanced CT was 88% vs. 50%, respectively. Statistically, PET/CT and CT were equivalent for nodal disease, but PET/CT was more accurate for extranodal disease. (9) In a meta-analysis of 20 studies, PET/CT had a pooled sensitivity of 90.9% (95% CI, 88.0-93.4) and the pooled false-positive rate was 10.3% (95% CI, 7.4-13.8). (10) Change in treatment has been reported in as many as 9% of cases with the addition of PET/CT scan. (11)
 
For acute leukemia, CT scans of the neck, chest, and abdomen/pelvis with IV contrast and CT or MRI head are recommended as indicated by signs/symptoms at diagnosis; PET/CT may be considered if any extramedullary involvement is suspected. (1, 2)
 
MANAGEMENT
In general, advanced imaging is not necessary for routine monitoring of treatment response or progression of CLL/SLL. A meta-analysis of the German CLL study group phase 3 trials (CLL4, CLL5, and CLL8) found that 77% of recurrent/progressive disease were detected by clinical symptoms or laboratory testing; CT detected an additional 9% with only a 1% effect on management decisions. (12)
 
The 5-point Deauville criteria are used for assessment of treatment response. In a retrospective study, PET/CT outperformed CT for response assessment for follicular non-Hodgkin lymphoma. The accuracy of PET/CT for response assessment was superior to CT (0.97 vs 0.64) and also predicted improvement in progression-free survival (48 months vs 17 months, P <.01). (13)
 
Multiple studies have confirmed that PET positivity correlates with active tumor for both NHL and lymphomatous extramedullary disease in ALL. In a representative study, patients who had negative PET imaging after 2 cycles of therapy had a higher rate of complete remission (83% vs 58%) and greater estimated 2 year overall survival (90% vs 61%, P < .001). (14) A more recent prospective study, however, showed that a positive interim PET scan predicted worse event-free survival (48% vs 74%, P =.004), but was unable to predict differences in 2 year overall survival (88% vs 91%, P < .001). (15)
 
SURVEILLANCE
For CLL/SLL, routine use of CT is not indicated. Management changes resulting from CT imaging only occurred in 1% of patients.12 There is limited data to support routine surveillance imaging in indolent NHL. A retrospective study assessing CT for patients who had achieved complete remission found that only 4% of relapses were detected on surveillance imaging. (16) In a study looking at the use of PET/CT surveillance, relapse was found in 30% of asymptomatic patients. Sixteen percent of patients had no evidence of relapse by CT imaging. The value of PET for early detection of relapse is still under active investigation. (17)
 
There is limited data to support routine surveillance imaging in aggressive or highly aggressive NHL. A retrospective study assessing CT in patients who had achieved complete remission found that only 6% of relapses were detected on surveillance imaging. (18) In a prospective trial including patients with indolent, intermediate, and aggressive NHL, PET/CT surveillance detected relapses in 27% of patients. (17) In a recent population-based study, PET/CT only detected 2% of asymptomatic relapse. (19) Cohen et al. found that surveillance imaging did not detect most relapses prior to clinical signs and symptoms, and the imaging findings did not result in improved survival. (20)
 
Current References
    1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (Version 2.2020). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.
    2. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia (Version 3.2021). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.
    3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 3.2021). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.
    4. Weiler-Sagie M, Bushelev O, Epelbaum R, et al. (18)F-FDG avidity in lymphoma readdressed: a study of 766 patients. J Nucl Med. 2010;51(1):25-30. PMID: 20009002
    5. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas (Version 3.2021). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.
    6. Gomez Leon N, Delgado-Bolton RC, Del Campo Del Val L, et al. Multicenter comparison of contrast-enhanced FDG PET/CT and 64-slice multi-detector-row CT for initial staging and response evaluation at the end of treatment in patients with lymphoma. Clin Nucl Med. 2017;42(8):595-602. PMID: 28604477
    7. Blum RH, Seymour JF, Wirth A, et al. Frequent impact of [18F]fluorodeoxyglucose positron emission tomography on the staging and management of patients with indolent non-Hodgkin's lymphoma. Clin Lymphoma. 2003;4(1):43-9. PMID: 12837154
    8. Wohrer S, Jaeger U, Kletter K, et al. 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) visualizes follicular lymphoma irrespective of grading. Ann Oncol. 2006;17(5):780-4. PMID: 16497824
    9. Schaefer NG, Hany TF, Taverna C, et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging--do we need contrast-enhanced CT? Radiology. 2004;232(3):823-9. PMID: 15273335
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    14. Haioun C, Itti E, Rahmouni A, et al. [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood. 2005;106(4):1376-81. PMID: 15860666
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2022 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2022. No new literature was identified that would prompt a change in the coverage statement.
 
NCCN Guidelines for Acute Lymphoblastic Leukemia (Version 2.2022), Acute Myeloid Leukemia (Version 2.2022), and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 2.2022) were reviewed.   
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through November 2023. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
78811Positron emission tomography (PET) imaging; limited area (eg, chest, head/neck)
78812Positron emission tomography (PET) imaging; skull base to mid thigh
78813Positron emission tomography (PET) imaging; whole body
78814Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; limited area (eg, chest, head/neck)
78815Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; skull base to mid thigh
78816Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; whole body
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