The combined role of biomarkers and interim PET scan in prediction of treatment outcome in classical Hodgkin's lymphoma: a retrospective, European, multicentre cohort study

Agostinelli, Claudio; Gallamini, Andrea; Stracqualursi, Luisa; Agati, Patrizia; Tripodo, Claudio; Fuligni, Fabio; Sista, Maria Teresa; Fanti, Stefano; Biggi, Alberto; Vitolo, Umberto; Rigacci, Luigi; Merli, Francesco; Patti, Caterina; Romano, Alessandra; Levis, Alessandro; Trentin, Livio; Stelitano, Caterina; Borra, Anna; Piccaluga, Pier Paolo; Hamilton-Dutoit, Stephen; Kamper, Peter; Zaucha, Jan Maciej; Małkowski, Bogdan; Kulikowski, Waldemar; Tajer, J.; Subocz, Edyta; Rybka, Justyna; Steidl, Christian; Broccoli, Alessandro; Argnani, Lisa; Gascoyne, Randy D.; d’Amore, Francesco; Zinzani, Pier Luigi; Pileri, Stefano

doi:10.1016/s2352-3026(16)30108-9

Cited by 64 publications

(57 citation statements)

References 28 publications

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“…Some studies are exploring the combination of interim-PET results with additional parameters derived from baseline imaging [25], or from lymphoma tissue analysis and biological biomarkers [26][27][28][29]. One team showed that textural analysis of baseline CT images are correlated to progression-free survival and can be combined with information from interim-PET [30].…”

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confidence: 99%

“…Numerous biomarkers within the Reed-Sternberg cell and its microenvironment can also be exploited [33]. Agostinelli and colleagues recently analyzed the prognostic value of a set of three immunochemistry markers: STAT1, CD68 and PD-1 [27]. Following a regression tree analysis of a training set of patients, they successfully individualized a high-risk group that predicts failure within interim PET-negative patients.…”

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confidence: 99%

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Advanced Hodgkin’s lymphoma: End-of-treatment FDG-PET should be maintained

Hindié

Mesguich

Bouabdallah

et al. 2017

Eur J Nucl Med Mol Imaging

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confidence: 99%

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confidence: 99%

Advanced Hodgkin’s lymphoma: End-of-treatment FDG-PET should be maintained

Hindié

Mesguich

Bouabdallah

et al. 2017

Eur J Nucl Med Mol Imaging

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“…Patients with positive interim 18 F-FDG PET/CT results had a dismal progression-free survival of 12.8% in one study and 28% in the other, whereas patients with negative interim 18 F-FDG PET/CT results had an excellent progression-free survival of 95% in both studies after finishing standard ABVD therapy (12,13). 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).…”

Section: Replymentioning

confidence: 97%

“…We individually criticized all 3 of these studies for these issues (27)(28)(29). On the other hand, multiple, recently published, large-scale studies (14,(24)(25)(26) unambiguously showed that (in contrast to the studies by Gallamini et al (12,13)) a high proportion of the large group of patients with negative interim 18 F-FDG PET/CT results develops disease relapse during follow-up and that, therefore, a negative interim 18 F-FDG PET/CT result cannot exclude residual disease. In other words, most relapses occur after a negative interim 18 F-FDG PET/CT result (14,(24)(25)(26).…”

Section: Replymentioning

confidence: 99%

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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“…In a study of 310 HL patients, the expression of neoplastic cell-associated and microenvironment-associated biomarkers such as CD68, PD-1, and STAT-1 allowed for the reclassification of PET2 patients as either low-risk or high-risk, with corresponding 3-y PFS values of 95% and 63%, respectively (35). Similarly, bcl-2 expression has served as a complement to interim PET in NHL patients, helping to stratify risk.…”

Section: Future Trends In Interim Response Assessmentmentioning

confidence: 99%

Response Assessment Criteria and Their Applications in Lymphoma: Part 2

et al. 2016

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Learning Objectives: On successful completion of this activity, participants should be able to describe (1) the diagnostic and predictive value of interim and end-of-treatment PET in HL and NHL; (2) the role of response-adapted therapy in the clinical management of lymphoma; and (3) the newly-emerging applications of interim and end-of-treatment PET in lymphoma.Financial Disclosure: The authors of this article have indicated no relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through January 2020.Interim and end-of-treatment PET/CT have become central to the evaluation of Hodgkin and non-Hodgkin lymphoma. This review article seeks to aid clinical decision making by providing an overview of available data on the diagnostic and prognostic value of PET/CT imaging for response assessment and pretransplant evaluation in lymphoma. The relative strengths and limitations of these techniques in various disease subtypes and clinical scenarios are explored, along with their current standards for reporting and latest developments. Particular attention is given to response-adapted therapy, which is emerging as a cornerstone of clinical management. CTandPETwi th 18 F-FDG have come to play integral roles in evaluating Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Soon after the incorporation of CT into staging and response assessment criteria, the advantages of using PET's metabolic data in conjunction with CT's structural information for these applications began to become apparent. This combination was especially helpful in the staging and restaging of lymphoma. It was shown to reliably identify the 80%-95% of posttreatment residual masses that are nonmalignant, thereby sparing patients unnecessary therapy and morbidity, and it was shown to alter staging in 20% of cases, most frequently upstaging patients by better detecting bone marrow involvement (1,2).After the integration of PET into the International Working Group criteria in 2007, PET/CT was widely adopted as a first-line imaging tool for evaluating end-of-treatment response in lymphoma (3). Subsequent studies laid the groundwork for the Deauville 5-point scale (D5PS) criteria, designed for the visual interpretation of PET scans (4). This was expanded by the Lugano guidelines, which established PET/CT as the modality of choice for staging and response assessment in 18 F-FDG-avid subtypes of lymphoma but maintained CT as the preferred tool for the small histologic subset with low or variable avidity (5). These guidelines are pa...

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The combined role of biomarkers and interim PET scan in prediction of treatment outcome in classical Hodgkin's lymphoma: a retrospective, European, multicentre cohort study

Cited by 64 publications

References 28 publications

Advanced Hodgkin’s lymphoma: End-of-treatment FDG-PET should be maintained

Advanced Hodgkin’s lymphoma: End-of-treatment FDG-PET should be maintained

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

Response Assessment Criteria and Their Applications in Lymphoma: Part 2

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