Proportion of false-positive lesions at interim and end-of-treatment FDG-PET in lymphoma as determined by histology: Systematic review and meta-analysis

Adams, Hugo J. A.; Kwee, Thomas C.

doi:10.1016/j.ejrad.2016.08.011

Cited by 70 publications

(61 citation statements)

References 24 publications

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“…Second, we believe the title of their article does not reflect their findings, in which they report FDG‐avidity to be synonymous to residual lymphoma (‘ can residual PET‐positive disease be cured with radiotherapy alone?’ ) despite their finding that 2/3 (66%) of cases of residual FDG‐avid lesions appeared to be false‐positive when biopsy was performed. Note that the high false‐positive rate at response evaluation scans in Hodgkin lymphoma has be reported before (Adams & Kwee, , ), with inflammation being responsible for FDG‐avidity in the majority of cases. The fact that post‐ABVD FDG‐PET results alone have a low positive predictive value (PPV) in predicting disease relapse, and biopsy results do clearly predict a dismal prognosis, suggest that false‐positive results are common at post‐ABVD FDG‐PET scans.…”

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confidence: 62%

Post‐ABVD biopsy results, and not post‐ABVD FDG‐PET results, predict outcome in early‐stage Hodgkin lymphoma

Adams

Kwee

2017

Br J Haematol

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We read with interest the recently published article by Milgrom et al (2017) entitled 'Early-stage Hodgkin lymphoma outcomes after combined modality therapy according to the post-chemotherapy 5-point score: can residual pet-positive disease be cured with radiotherapy alone?'. Their study included 174 patients with early-stage (I-II) Hodgkin lymphoma treated with ABVD (doxorubicin, bleomycin, vincristine; dacarbazine; median 4 cycles, range 2-6) followed by an 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scan. Patients were treated with additional radiation therapy (RT) regardless of FDG-PET findings. The prognostic value of post-ABVD FDG-PET results according to the Deauville criteria and several quantitative FDG-PET biomarkers (table IV in Milgrom et al, 2017) was evaluated. After ABVD therapy, 5-year progression-free survival (PFS) was 100% (0 relapses/98 patients) in patients with Deauville scores of 1-2, 97% (2/65) for a Deauville score of 3, 83% (1/ 8) for a Deauville score of 4 and 67% (1/3) for a Deauville score of 5. Three of 11 (27Á3%) patients with positive FDG-PET results (i.e. Deauville score ≥4) underwent biopsy of residual FDG-avid lesions. FDG-PET results were false-positive in 2/3 (66%), with biopsy showing no lymphoma, whereas biopsy revealed residual lymphoma in 1/3 (33%) cases. This particular patient developed disease relapse during follow-up. On the other hand, none of the FDG-PET metrics was able to differentiate between relapsing and non-relapsing patients. The results were compared with a very selective group (inclusion criteria for this cohort not clearly described in the methods section) of 15 Hodgkin lymphoma patients treated with additional salvage chemotherapy and autologous stem cell transplantation (ASCT). Of these 15 patients, 13 had undergone post ABVD biopsy, with 13 of these biopsies (100%) showing residual lymphoma, highly contrasting the results of the other cohort, in which biopsy showed no lymphoma in the majority of cases. Despite intensive treatment with ASCT, 6/15 (40%) Hodgkin lymphoma patients developed disease relapse during follow-up. Comparison between these two cohorts revealed FDG-PET metrics to be more or less similar in both groups (table III in Milgrom et al, 2017), despite the clearly different prognosis of patients included in these two cohorts. Moreover, despite Milgrom et al.'s statement that the 15 patients treated with intensive therapies all suffered from stable or progressive disease, the reduction in FDG-PET metrics in this cohort was notable (Table III in Milgrom et al, 2017). On the other hand, a strong significant difference (P < 0Á001) between these two cohorts was the presence of a post-ABVD lymphoma-positive biopsy (table III in Milgrom et al, 2017). The authors concluded that a positive post-ABVD FDG-PET scan was associated with inferior PFS, but the majority of patients with positive FDG-PET results were considered to be curable with RT alone.However, we disagree with their interpretations. First, we believe the conclus...

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confidence: 62%

Post‐ABVD biopsy results, and not post‐ABVD FDG‐PET results, predict outcome in early‐stage Hodgkin lymphoma

Adams

Kwee

2017

Br J Haematol

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“…The fact that Hodgkin lymphoma is a highly curable disease with a low relapse rate, in combination with the low sensitivity of end‐of‐treatment FDG‐PET, underlines that the number needed to scan (i.e., number of end‐of‐treatment FDG‐PET scans required to detect one case with residual disease) is very high. Furthermore, FDG‐PET scans are expensive, use ionizing radiation, provide patient discomfort, are not available in all institutions and generate false‐positive findings (Adams & Kwee, ; Mesguich et al , ). The latter can have serious consequences, such as unjustified changes in therapy management and prognostication (if histological confirmation of residual FDG‐avid lesions is not performed), result in a high number of unnecessary biopsies, and cause patient anxiety.…”

Section: Results Of Studies On the Sensitivity Of End‐of‐treatment Fdmentioning

confidence: 99%

Hodgkin lymphoma: is there really a need for interim and end‐of‐treatment FDG‐PET evaluations?

Adams

Kwee

2016

Br J Haematol

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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.…”

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confidence: 86%

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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Proportion of false-positive lesions at interim and end-of-treatment FDG-PET in lymphoma as determined by histology: Systematic review and meta-analysis

Cited by 70 publications

References 24 publications

Post‐ABVD biopsy results, and not post‐ABVD FDG‐PET results, predict outcome in early‐stage Hodgkin lymphoma

Post‐ABVD biopsy results, and not post‐ABVD FDG‐PET results, predict outcome in early‐stage Hodgkin lymphoma

Hodgkin lymphoma: is there really a need for interim and end‐of‐treatment FDG‐PET evaluations?

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

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