Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs

El‐Galaly, Tarec Christoffer; Mylam, Karen Juul; Brown, Peter de Nully; Specht, Lena; Christiansen, Ilse; Munksgaard, Lars; Johnsen, Hans Erik; Loft, Annika; Bukh, Anne; Iyer, Victor Vishwanath; Nielsen, Anne Lerberg; Hutchings, Martin

doi:10.3324/haematol.2011.056010

Cited by 75 publications

(78 citation statements)

References 25 publications

(35 reference statements)

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“…However, both studies had a major (12)(13)(14)(15). Posttreatment and follow-up 18 F-FDG PET/CT studies have a strikingly high number of false-positive results, as has been reported for several lymphoma subtypes (16)(17)(18)(19), including Hodgkin lymphoma (20). Consequently, the studies by Gallamini et al (12,13) are methodologically seriously biased.…”

Section: Replymentioning

confidence: 83%

Reply: Interim PET in Hodgkin Lymphoma: Is It So Useless?

Adams

Kwee²

2017

J Nucl Med

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More than 2,000 patients with advanced disease were included in 3 well-designed prospective trials, in which patients who-after 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-were PET-positive (Deauville score $ 4) were escalated to BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) whereas those who were PET-negative continued with the standard regimen (4 cycles of ABVD) (1-3). The PET positivity rate using this Deauville score as the cutoff was similar across these 3 studies, as was the outcome of both PET-positive and PET-negative patients. The study of the Southwest Oncology Group (1) enrolled 336 patients, 18% of whom were PET-positive. The "Response Adapted Therapy in Advanced Hodgkin Lymphoma" study (2) enrolled 1,119 patients, 25% of whom were PET-positive. The Italian GITIL/FIL HD0607 trial (3) enrolled 773 patients, 19% of whom were PET-positive. Overall, the 2-y progression-free survival of the PET-positive patients ranged between 64% and 67%. PET-negative patients who followed the standard regimen had a 2-y progression-free survival ranging between 82% and 89%, higher than the progression-free survival of the whole population.A major advantage of this strategy is that PET-negative patients (.80% of the total population) can be spared from the adverse effects of BEACOPP. As pointed out by Adams and Kwee, none of the interim 18 F-FDG PET/CT-adapted trials that have been performed so far had a control arm; that is, none continued standard ABVD in PET-positive patients. Apart from the fact that this arm would have been ethically difficult to defend, series have found 2-y progression-free survivals of 12%-27% in advanced-stage Hodgkin lymphoma patients PET-positive after 2 ABVD cycles-much lower than the 64%-67% found when these patients were intensified with BEACOPP (4,5), with this strategy therefore clearly having an advantage in improving outcome and decreasing the number of events. This finding was further confirmed by the results of the EORTC/LYSA/FIL H10 trial (6), which included 1,950 patients with early-stage Hodgkin lymphoma randomized between an experimental arm and a standard arm. Patients PET-positive after 2 ABVD cycles had a 5-y progression-free survival of 77.4% in the experimental arm that received standard ABVD plus involved-node radiotherapy, and survival improved to 90.6% in the experimental arm that received BEACOPP escalation plus involved-node radiotherapy (hazard ratio, 0.42; 95% confidence interval, 0.23-0.74; P 5 0.002).A deescalation trial (7) in 823 patients with advanced Hodgkin lymphoma (AHL2011 LYSA trial) has also recently confirmed the major role of an interim PET-guided strategy. Patients PETnegative after 2 BEACOPP escalations were moved to ABVD. Their progression-free survival was not inferior to that of the standard arm, in which BEACOPP was continued. Thus, deescalation avoids the toxic effect of BEACOPP while producing the same outcome.In view of the cited evidence, we strongly disagree with A...

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Section: Replymentioning

confidence: 83%

Reply: Interim PET in Hodgkin Lymphoma: Is It So Useless?

Adams

Kwee²

2017

J Nucl Med

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“…Likewise, recent research is providing a growing body of evidence of the limitations in PET-CT usage in follow-up. For instance, a substantial number of false-positive PET-CT results was revealed in routine surveillance among patients who had achieved remission after first-line therapy, which is particularly unfortunate considering the high costs involved [21]. Maeda et al also reported that PET-CT has low positive predictive value in surveillance [22].…”

Section: Discussionmentioning

confidence: 99%

Positron Emission Tomography Scanning in the Management of Hodgkin Lymphoma Patients: A Single-Institution Experience

2016

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“…7 Even with its relatively high sensitivity, the risks and benefits of routine surveillance PET/CT imaging remain controversial, mainly, because of its cost, radiation burden and the high rate of false-positive results (30-80%) 3,[8][9][10][11][12] with potential consequences of overtreatment. In this issue of the Journal, El-Galaly et al report the value of surveillance PET/CT in a retrospective cohort of 161 HL patients who achieved a complete or partial remission after first-line treatment.…”

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“…In this issue of the Journal, El-Galaly et al report the value of surveillance PET/CT in a retrospective cohort of 161 HL patients who achieved a complete or partial remission after first-line treatment. 12 During a median follow-up of 34 months 14% of patients experienced a relapse. With an average of 1.9 PET/CT per patient, the positive predictive value (PPV) of routine PET/CT and clinically indicated PET/CT was 22% and 37%, respectively (P=0.02).…”

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“…While PET/CT has not been closely investigated in a surveillance setting, it has become clear that its accuracy is superior to that of CT imaging. According to results from a meta-analysis, FDG-PET predicts disease relapse with a sensitivity and specificity of 50-100% and 67-100%, respectively, for HL and 33-77% and 82-100%, respectively, for NHL, irrespective of the association of a residual mass on CT. 7 Even with its relatively high sensitivity, the risks and benefits of routine surveillance PET/CT imaging remain controversial, mainly, because of its cost, radiation burden and the high rate of false-positive results (30-80%) 3,[8][9][10][11][12] with potential consequences of overtreatment. In this issue of the Journal, El-Galaly et al report the value of surveillance PET/CT in a retrospective cohort of 161 HL patients who achieved a complete or partial remission after first-line treatment.…”

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Positron emission tomography/computed tomography surveillance in patients with lymphoma: a fox hunt?

Gallamini¹,

Kostakoglu²

2012

Haematologica

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Despite improvements in survival rates, relapses after first-line therapy can occur in 20-50% of patients with advanced-stage Hodgkin's lymphoma (HL) or diffuse large-B-cell lymphoma (DLBCL).1,2 In both diseases, treatment failures are usually observed within 3 years of completion of treatment with the majority of relapses occurring in the first 12 months for HL 3,4 and 18 months for DLBCL. 4 However, no consensus exists on an optimal surveillance strategy to determine a preclinical relapse after first remission, although routine [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging has become a standard practice in many centers. The benefits of monitoring for recurrence depend on the probability of relapse in the population being tested as well as the sensitivity, specificity and the frequency of the test. 5 The prevalence of relapse in both HL and DLBCL is rare, with reportedly only one relapse per 68 visits in HL 6 and per 40-45 visits for patients with aggressive non-Hodgkin's lymphoma (NHL) 5 based on routine CT scans. While PET/CT has not been closely investigated in a surveillance setting, it has become clear that its accuracy is superior to that of CT imaging. According to results from a meta-analysis, FDG-PET predicts disease relapse with a sensitivity and specificity of 50-100% and 67-100%, respectively, for HL and 33-77% and 82-100%, respectively, for NHL, irrespective of the association of a residual mass on CT.7 Even with its relatively high sensitivity, the risks and benefits of routine surveillance PET/CT imaging remain controversial, mainly, because of its cost, radiation burden and the high rate of false-positive results (30-80%) 3,[8][9][10][11][12] with potential consequences of overtreatment. In this issue of the Journal, El-Galaly et al. report the value of surveillance PET/CT in a retrospective cohort of 161 HL patients who achieved a complete or partial remission after first-line treatment.12 During a median follow-up of 34 months 14% of patients experienced a relapse. With an average of 1.9 PET/CT per patient, the positive predictive value (PPV) of routine PET/CT and clinically indicated PET/CT was 22% and 37%, respectively (P=0.02). However, in a subset of high-risk patients (with extranodal disease, a positive PET result at interim or therapy completion) the PPV increased to 36% while in those without risk factors the PPV was only 5%. Consequently, the authors concluded that the routine use of surveillance PET in HL patients entering complete remission after first-line treatment should be reserved for high-risk patients. These results were in line with those of Petrausch et al. who suggested that monitoring may be worthwhile in high-risk DLBCL populations. 11The weaknesses of the existing surveillance PET studies include retrospective design, the paucity of prospective data in distinct risk categories, non-standardized interpretation of PET/CT, and the lack of randomized multicenter setting, while the strength is that all data were obtained afte...

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Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs

Cited by 75 publications

References 25 publications

Reply: Interim PET in Hodgkin Lymphoma: Is It So Useless?

Reply: Interim PET in Hodgkin Lymphoma: Is It So Useless?

Positron Emission Tomography Scanning in the Management of Hodgkin Lymphoma Patients: A Single-Institution Experience

Positron emission tomography/computed tomography surveillance in patients with lymphoma: a fox hunt?

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