Coverage Policy Manual
Policy #: 2013002
Category: Radiology
Initiated: January 2013
Last Review: December 2021
  PET or PET/CT for Hodgkin's Lymphoma

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.  Additionally, lesions < 1 cm are not reliably visualized with PET.  PET/CT has largely replaced dedicated PET in the United States.  
 
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.
 
RELATED POLICY:
    • 2000002 - PET for non-Hodgkin's Lymphoma
 
 

Policy/
Coverage:
EFFECTIVE MARCH 13, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
FDG-PET/CT for patients with Hodgkin’s Lymphoma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Diagnostic Workup:
        • (As clinically) Indicated   
Management:
Indicated in ANY of the following scenarios:
        • Radiation planning for definitive or consolidative treatment
        • Evaluation of response following 2-4 cycles of treatment
        • Baseline post-treatment evaluation at least 3 weeks following completion of all cycles of chemotherapy or 12 weeks following completion of radiation therapy
        • Single follow up when first post-treatment baseline PET showed Deauville 4 or 5 findings*
        • Clinical suspicion for recurrence or progression of disease based on standard imaging or objective signs/symptoms
 
*Deauville 4 (uptake moderately increased compared to the liver at any site); Deauville 5 (uptake
markedly increased compared to the liver at any site)
 
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 Hodgkin’s Lymphoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
    • Surveillance*
For members with contracts without primary coverage criteria, PET/CT for patients with Hodgkin Lymphoma 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 Plan exclusions.
 
 
*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 Prior to MARCH 13, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
FDG-PET/CT for patients with Hodgkin’s Lymphoma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Diagnostic Workup  
    • As clinically indicated.
Treatment Management
Indicated in ANY of the following scenarios:
      • Radiation planning for definitive or consolidative treatment; or
      • Evaluation of response following 2-4 cycles of treatment; or
      • Baseline post-treatment evaluation at least 3 weeks following completion of all cycles of chemotherapy or 12 weeks following completion of radiation therapy; or
      • Post-treatment follow-up when post-treatment baseline was Deauville 4 or 5 ; or
      • Clinical suspicion for 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 Hodgkin’s Lymphoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
    • For screening and surveillance: or
    • For any other indication not specifically listed above.
 
*For fully-insured contracts subject to Act 583 of Arkansas legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
PET/CT for patients with Hodgkin’s Lymphoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
    • For screening and surveillance: or
    • For any other indication not specifically listed above.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
 
Effective Prior to August 2021
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
FDG-PET/CT for patients with Hodgkin’s Lymphoma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Diagnostic Workup
 
As clinically indicated.
 
Treatment Management
 
Indicated in ANY of the following scenarios:
 
      • Radiation planning for definitive or consolidative treatment; or
      • Evaluation of response following 2-4 cycles of treatment; or
      • Baseline post-treatment evaluation at least 3 weeks following completion of all cycles of chemotherapy or 12 weeks following completion of radiation therapy; or
      • Post-treatment follow-up when post-treatment baseline was Deauville 4 or 5 ; or
      • Clinical suspicion for 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 Hodgkin’s Lymphoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
      • For screening and surveillance: or
      • For any other indication not specifically listed above.
 
For members with contracts without primary coverage criteria, PET/CT for patients with Hodgkin’s Lymphoma is considered investigational:
 
      • For screening and surveillance; or
      • For any other indication not specifically listed above.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 2017 to June 15, 2021
 
The use of the term PET in this policy refers to PET or PET/CT using the radiotracer FDG.
 
PET scanning meets member certificate of benefit Primary Coverage Criteria for effectiveness for patients with a diagnosis of Hodgkin’s lymphoma:
    • For initial staging of their disease.
    • For restaging 6-8 weeks after completion of a planned course of therapy.
    • For restaging of patients with symptoms of recurrent disease.
    • For restaging after completion of chemotherapy for patients with stage IA-IIA (favorable disease) prior to planned radiation therapy
    • For restaging after 4 cycles of therapy for patients with stage I-II (unfavorable, bulky or non-bulky disease) as a prognostic indicator of treatment outcome
    • Restaging after 2 cycles of therapy for patients with advanced-stage disease (stage II disease with unfavorable risk factors [with or without bulky disease] or stage III-IV disease) as a prognostic indicator of treatment outcome.
 
PET scan imaging does not meet member certificate of benefit Primary Coverage Criteria for effectiveness for patients with Hodgkin’s lymphoma for:
    • Monitoring of treatment response because there is not enough evidence to indicate this testing improves health outcomes.
    • Surveillance since PET for surveillance remains controversial and further studies are needed to determine its role.
    • Diagnosis 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 covered for:
    • For initial staging of their disease.
    • For restaging 6-8 weeks after completion of a planned course of therapy.
    • For restaging of patients with symptoms of recurrent disease.
    • For restaging after completion of chemotherapy for patients with stage IA-IIA (favorable disease) prior to planned radiation therapy
    • For restaging after 4 cycles of therapy for patients with stage I-II (unfavorable, bulky or non-bulky disease) as a prognostic indicator of treatment outcome
    • Restaging after 2 cycles of therapy for patients with advanced-stage disease (stage II disease with unfavorable risk factors [with or without bulky disease] or stage III-IV disease) as a prognostic indicator of treatment outcome.
 
For those contracts without Primary Coverage Criteria, PET scanning is not covered for:
    • Monitoring of treatment response because there is not enough evidence to indicate this testing improves health outcomes.
    • Surveillance since PET for surveillance remains controversial and further studies are needed to determine its role.
    • Diagnosis as this use is specifically recommended against by major medical publications and national medical groups.
 
Investigational services are an exclusion in the member certificate of coverage.
 
PET scanning should not be done for imaging of tumors that are known not to be FDG-avid.
  
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)
 
EFFECTIVE PRIOR TO APRIL 2017
 
The use of the term PET in this policy refers to PET or PET/CT using the radiotracer FDG.
 
PET scanning meets member certificate of benefit Primary Coverage Criteria for effectiveness for patients with a diagnosis of Hodgkin’s lymphoma:
        • For initial staging of their disease.
        • For restaging 6-8 weeks after completion of a planned course of therapy.
        • For restaging of patients with symptoms of recurrent disease.
        • For restaging after completion of chemotherapy for patients with stage IA-IIA (favorable disease) prior to planned radiation therapy
        • For restaging after 4 cycles of therapy for patients with stage I-II (unfavorable, bulky or non-bulky disease) as a prognostic indicator of treatment outcome
 
PET scan imaging does not meet member certificate of benefit Primary Coverage Criteria for effectiveness for patients with Hodgkin’s lymphoma for:
        • Monitoring of treatment response because there is not enough evidence to indicate this testing improves health outcomes.
        • Surveillance since PET for surveillance remains controversial and further studies are needed to determine its role.
        • Diagnosis 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 covered for:
        • For initial staging of their disease.
        • For restaging 6-8 weeks after completion of a planned course of therapy.
        • For restaging of patients with symptoms of recurrent disease.
        • For restaging after completion of chemotherapy for patients with stage IA-IIA (favorable disease) prior to planned radiation therapy
        • For restaging after 4 cycles of therapy for patients with stage I-II (unfavorable, bulky or non-bulky disease) as a prognostic indicator of treatment outcome
 
For those contracts without Primary Coverage Criteria, PET scanning is not covered for:
        • Monitoring of treatment response because there is not enough evidence to indicate this testing improves health outcomes.
        • Surveillance since PET for surveillance remains controversial and further studies are needed to determine its role.
        • Diagnosis as this use is specifically recommended against by major medical publications and national medical groups.
 
Investigational services are an exclusion in the member certificate of coverage.
 
PET scanning should not be done for imaging of tumors that are known not to be FDG-avid.
  
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:
This policy is based on literature reviews that considered the use of PET scanning in the evaluation of lymphoma.
 
Lymphoma, including Hodgkin’s disease:
Of the 14 available studies, 3 compared PET with anatomic imaging in initial staging and restaging patients with Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma. Two of these studies included data from both diseased and nondiseased sites for PET and CT. Both studies found PET to have better overall diagnostic accuracy than CT. The third study addressed detection of diseased sites only and found PET to have the same sensitivity as use of CT or MRI. Among the 6 studies that reported on concordance between PET and other imaging modalities, PET was discordant with other modalities in 11% to 50%, PET was correct among discordances in 40% to 75%. PET has been reported to affect patient management decisions in 8%–20% of patients in 5 studies mainly by correctly upstaging disease, but also by correctly down staging disease. Thus when PET is added to conventional imaging, it can provide useful information for selective effective treatment that is appropriate to the correct stage of disease.
 
PET has been investigated for Diagnosis, Initial staging, Restaging, Monitoring, and Surveillance of 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.
 
Cronin and colleagues (2010)
•   PET/CT has greater sensitivity for sites of extranodal involvement and improves baseline staging compared with CT alone.
•   Because the stage of the disease is less important that the clinical manifestations, PET/CT is not used for routine staging.  In certain instances, however, PET/CT can be useful in the management of low-grad lymphoma.  PET/CT is important for excluding unexpected sites of nodal or extranodal lymphoma which would necessitate prolonged chemotherapy (six to eight cycles).
•   Hodgkin’s lymphoma is FDG avid, and PET/CT is a more accurate initial staging examination thatn conventional diagnostic CT, particularly for detection of unexpected sites of extranodal lymphoma.
•   In Hodgkin’s lymphoma, posttreatment PET/CT is used to confirm the success of treatment and exclude residual viable malignancy.  In patients with a poor prognostic index at baseline, it may be appropriate to perform PET/CT early in the course of therapy (e.g., after two to four cycles of chemotherapy) to detect refractory disease, the presence of which can influence subsequent treatment decisions.
•   In patients with early-stage Hodgkin’s lymphoma who have completed 6 to 8 cycles of standard therapy (with or without the addition of radiation), persistent FDG uptake indicates the presence of refractory disease and is associated with poor long-term survival.
•   In all cases, correct PET/CT interpretation depends on having an adequate knowledge of the clinical history, correlation with findings of other imaging studies, and familiarity with the wide range of potential imaging artifacts and interpretative pitfalls that can be encountered.
 
NCCN Guidelines for Hodgkin Lymphoma, Version 2.2012 were consulted in establishing limited coverage of interim response PET or PET/CT imaging Hodgkin Lymphoma.  
•   Stage I-II Unfavorable (Bulky) – Restage after 4 cycles  to assess response to therapy
•   Stage III-IV – restage after completion of chemotherapy to assess response to therapy
•   Surveillance PET should not be done routinely due to risk for false positives.  Management decisions should not be based on PET scan alone, clinical or pathological correlation is needed.
•   PET scans are recommended for initial staging and evaluating residual masses at the end of treatment.
•   Interim PET imaging is not of prognostic significance in patients with early stage disease.
•   The consensus of the panel was that there is not enough evidence to recommend interim PET scans for patients with stage I-II favorable disease.  Imaging after completion of chemotherapy is essential for radiation therapy planning for patients receiving combined modality treatment.
•   The panel acknowledges that guiding therapy based on the results of interim PET scans is considered investigational and is not recommended outside the context of clinical trial.
•   In 2 prospective studies, PET or PET/CT after 2 cycles of ABVD was a strong and independent prognostic factor of progression free survival in patients with advanced stage and extranodal disease.
 
 
The following ongoing and completed studies were found at www.clinicaltrials.gov:
•   NCT01248000 – “The Use of FDG-PET in Patient With Hodgkin Lymphoma: a Population Based Study From Northern Italy”_Retrospective; enrollment 136; study completed; results not yet published.
•   NCT01132807 – “Phase II Trial of Response-Adapted Chemotherapy Based on Positron Emission Tomography for Non-Bulky Stage I and II Hodgkin Lymphoma”¬_NCI sponsored; estimated enrollment 149 with completion date of June 2016.
•   NCT00887718 - Positron Emission Tomography for Staging, and Treatment Assessment of Response in Lymphomas (the PET-STAR Lymphoma Study)_(Canada); non-randomized interventional study with enrollment of 103.  Study completed, results not yet published.
 
•   NCT01304849 – “Phase II Study of Interim PET-CT Scan-guided Response Adapted Therapy in Hodgkin's Lymphoma”_(India) estimated enrollment 50 with completion date of September 2013.
 
2014 Update
A literature search was conducted through December 2013.  There was no new literature identified that would prompt a change in the coverage statement.
 
2017 Update
A literature search was conducted through March 2017. Following is a summary of the key literature.  
 
According to NCCN Guidelines for Hodgkin Lymphoma (NCCN, v1.2017), early interim PET imaging after chemotherapy has been shown to be a sensitive prognostic indicator of treatment outcome in patients with advanced-stage disease (stage II disease with unfavorable risk factors (with or without bulky disease) or stage III-IV disease).  
 
Radford et al (2015) conducted a randomized trial of 602 patients with newly diagnoses stage IA or stage IIA Hodgkin’s lymphoma who received three cycles of ABVD and then underwent PET scanning and was designed to assess the non-inferiority of no further treatment.  Patients with negative PET findings were randomly assigned to receive involved-field radiotherapy or no further treatment; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy. The authors concluded that:  
    • The results did not show non-inferiority of the strategy of no further treatment after chemotherapy with regard to PFS.  
    • Patients in the study with early-stage Hodgkin’s lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy.  
 
Terasawa et al (2009) performed a systematic review of the prognostic accuracy of FDG-PET for interim response assessment of patients with untreated advanced-stage Hodgkin's lymphoma (HL) or diffuse large B-cell lymphoma (DLBCL) and had the following conclusions:  
    • For low- to intermediate-risk advanced-stage HL, FDG-PET performed after a few cycles of standard chemotherapy seems to be a reliable prognostic test to identify poor responders, warranting prospective studies to assess PET-based treatment strategies.
    • For DLBCL, no reliable conclusions can be drawn due to heterogeneity. Interim PET remains an unproven test for routine clinical practice.
 
Avigdor et al (2010) performed a study on 45 newly diagnosed patients with advanced-stage HL and International Prognostic Score > or = 3.  The patients initially received two cycles of escBEACOPP and then were evaluated by positron emission tomography (PET)/computed tomography scan. If a good imaging response was obtained, they were treated by four cycles of ABVD.  Following the first two cycles of escBEACOPP, the overall response was 100% and at the end of all therapy. a median follow-up of 48 months, progression-free survival (PFS) and overall survival at 4 years were 78% and 95%, respectively. The 4-year PFS for early PET-negative patients were 87% and 53%, respectively.  The authors concluded that:  
    • Combined escBEACOPP-ABVD may improve the outcome in patients with high-risk advanced HL.
 
The potential benefit of early-interim PET activity as a guide to continuing therapy in these patients merits further study.
 
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.    
 
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.
 
DIAGNOSTIC WORKUP
Hodgkin lymphoma is staged using the Lugano classification system. PET/CT can result in changing of clinical stage in 20% of patients. (1) In the RATHL (Response-Adapted Therapy in Advanced Hodgkin Lymphoma) study, PET/CT resulted in upstaging 14% and downstaging 6%. (2) In a meta-analysis of 20 studies, the pooled sensitivity for PET/CT was 90.9% (95% CI, 88.0-93.4), and the pooled false positive rate was 10.3% (95% CI, 7.4-13.8) for staging and restaging.
 
MANAGEMENT
Response to treatment uses the 5-point Deauville criteria for assessment of metabolic response. For early-stage favorable Hodgkin lymphoma, the value of interim PET/CT has been mixed although more recent data supports the use of interim PET for response-adapted treatment. (3,4) For early-stage unfavorable Hodgkin lymphoma or stage III and IV Hodgkin lymphoma, Gallamini et al found that following a negative interim PET scan, the 2-year progression-free survival was 12.8% for PET positive and 95.0% for PET negative (P < .0001). (5) Cercil et al found 3-year event-free survival was 53.4% for PET positive and 90.5% for PET negative (P < 0.001). (6) Three large, randomized trials have confirmed that a risk-adapted approach to chemotherapy after negative interim PET is safe and did not result in poorer outcomes. (7,8)
 
SURVEILLANCE
There is limited data to support routine surveillance imaging in Hodgkin lymphoma. A randomized study comparing PET/CT to ultrasound and chest radiography for routine surveillance of patients with advanced Hodgkin lymphoma showed that sensitivity was equal in both groups. The conventional imaging arm had a higher specificity (96% vs 86%; P = .02) and positive predictive value (91% vs 73%; P = .01). (9) Although PET/CT negative patients had a high likelihood of being disease free, PET/CT also produced false positive rates as high as 20%. (10-12) A systematic review found no retrospective or prospective data demonstrating a survival advantage associated with the use of surveillance imaging for patients with Hodgkin lymphoma who achieved remission after first-line therapy. (13)
 
Current References
    1. Naumann R, Beuthien-Baumann B, Reiss A, et al. Substantial impact of FDG PET imaging on the therapy decision in patients with early-stage Hodgkin's lymphoma. British Journal of Cancer. 2004;90(3):620-5. PMID: 14760374
    2. Barrington SF, Kirkwood AA, Franceschetto A, et al. PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study. Blood. 2016;127(12):1531-8. PMID:26747247
    3. Andre MPE, Girinsky T, Federico M, et al. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Cl in Oncol.2017;35(16):1786-94. PMID: 28291393
    4. Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015;372(17):1598-607. PMID: 25901426
    5. Gallamini A, Hutchings M, Rigacci L, et al. Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced -stage Hodgkin's lymphoma: a report from a joint Italian-Danish study. J Clin Oncol. 2007;25(24):3746-52. PMID: 17646666
    6. Cerci JJ, Pracchia LF, Linardi CC, et al. 18F-FDG PET after 2 cycles of ABVD predicts event-free survival in early and advanced Hodgkin lymphoma.[Erratum appears in J Nucl Med. 2010 Oct;51(10):1658]. J Nucl Med.2010;51(9):1337-43. PMID: 20720036
    7. Bartlett NL. Fine-tuning the treatment of Hodgkin's lymphoma. N Engl J Med. 2016;374(25):2490-2. PMID:27332908
    8. Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med. 2016;374(25):2419-29. PMID: 27332902
    9. Picardi M, Pugliese N, Cirillo M, et al. Advanced-stage Hodgkin lymphoma: US/chest radiography for detection of relapse in patients in first complete remission--a randomized trial of routine surveillance imaging procedures. Radiology. 2014;272(1):262-74. PMID: 24708193
    10. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059-68. PMID: 25113753
    11. El-Galaly TC, Mylam KJ, Brown P, et al. Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs. Haematologica. 2012;97(6):931-6. PMID: 22207683
    12. Mocikova H, Obrtlikova P, Vackova B, et al. Positron emission tomography at the end of first-line therapy and during follow-up in patients with Hodgkin lymphoma: a retrospective study. Ann Oncol. 2010;21(6):1222-7. PMID:19901011
    13. Cohen JB, Behera M, Thompson CA, et al. Evaluating surveillance imaging for diffuse large B-cell lymphoma and Hodgkin lymphoma. Blood. 2017;129(5):561-4. PMID: 27956385
 
 

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

References: Avigdor A, et al.(2010) Two cycles of escalated BEACOPP followed by four cycles of ABVD utilizing early-interim PET/CT scan is an effective regimen for advanced high-risk Hodgkin's lymphoma. Ann Oncol 2010; 21:126-132.

Buchmann I, Reinhardt M, Eisner K, et al.(2001) 2 (fluorine 18) fluoro-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma.A bicenter trial. Cancer, 2001; 91; 889-899.

Cheson B.(2007) Revised response criteria for malignant lymphoma. J Clin Oncol, 2007; 25:579-586.

Cheson B.(2009) The case against heavy PETing. J Clin Oncol, 2009; 27:1742-1743.

Dupuis J.(2009) Response assessment after an inductive CHOP or CHOP-like regiment with or without rituximab in 103 patients with diffuse large B cell lymphoma integrating 18fluro-deoxyglucose positron emission tomography to the International Workshop Criteria. Ann Oncol, 2009; 20:503-507.

Jerusalem G.(2003) Early detection of relapse by whole body emission tomography in the follow-up of patients with Hodgkin’s Disease. Ann Oncol, 2003; 14:123-130.

Juweid ME(2006) Utility of positron emission tomography (PET) scanning in managing patients with Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2006:259-65, 510-1.

Juweid ME, Cheson BD.(2006) Positron-emission tomography and assessment of cancer therapy. N Engl J Med. 2006 Feb 2;354(5):496-507.

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