Diagnostische Wertigkeit von [18F]FDG-PET und Knochenmarkbiopsie bei Patienten mit Hodgkin-Lymphom

Die 2-[18F]Fluor-2-desoxy-D-glucose ([18F]FDG)-Positronenemissionstomographie (PET) konnte sich beim Staging des Hodgkin-Lymphoms als therapierelevante bildgebende Methode etablieren. Um festzustellen, ob Knochenmarkbiopsien adäquat durch eine PET zu ersetzen sind, haben wir die diagnostische Wertigkeit der [18F]FDG-PET mit den Ergebnissen des Biopsieverfahrens verglichen. In unsere Analyse wurden alle bis zum 31. Dezember 2015 für die HD16-, HD17- sowie HD18-Studie der Deutschen Hodgkin Studiengruppe (German Hodgkin Study Group, GHSG) rekrutierten Patienten eingeschlossen, bei denen initial sowohl eine Knochenmarkbiopsie als auch [18F]FDG-PET erfolgt war. Im Zuge der PET-Auswertung stuften wir das Knochenmark zunächst als fokal befallen oder unauffällig ein. Sofern eine Knochenmarkbeteiligung festzustellen war, erfolgte zusätzlich die Dokumentation von Läsionsanzahl und -lokalisation. Eine oberhalb des Leberuptakes gelegene diffuse [18F]FDG-Aufnahme haben wir aufgezeichnet, jedoch nicht als Befall gewertet. Im Zuge der Ausbreitungsdiagnostik durchliefen insgesamt 832 Studienteilnehmer eine [18F]FDG-PET-Untersuchung, welche dem zentralen GHSG-Referenzpanel vorlag. Bei 19 der 20 Patienten mit positiver Knochenmarkbiopsie ließen sich [18F]FDG-avide Knochenmarkherde identifizieren. Darüber hinaus stellten wir anhand der PET-Bildgebung 110 weitere Knochenmarkbeteiligungen fest, die mittels Biopsie nicht aufgefallen waren. Von den 129 Patienten mit fokalen Knochenmarkläsionen in der [18F]FDG-PET zeigten 43 ein unifokales Befallsmuster, 17 ein bifokales, 11 ein trifokales sowie 58 ein multifokales. Zusätzlich wurde in 152 Fällen eine diffus gesteigerte [18F]FDG-Aufnahme des Knochenmarks dokumentiert. Sofern man neben der Knochenmarkbiopsie ebenso die PET als Referenzstandard berücksichtigt, erzielte letztere im Rahmen unserer Studie eine Sensitivität sowie Spezifität von 99,2 (95 %-Konfidenzintervall [KI]: 95,8 – 100) bzw. 100 % (95 %-KI: 99,5 – 100) und einen positiv sowie negativ prädiktiven Wert von 100 (95 %-KI: 97,2 – 100) bzw. 99,9 % (95 %-KI: 99,2 – 100). Die [18F]FDG-PET identifizierte im untersuchten Patientenkollektiv eine hohe Anzahl von Knochenmarkbeteiligungen, welche bei der Biopsie nicht auffallen waren. Angesichts ihres hohen negativ prädiktiven Werts ist die PET ein geeignetes diagnostisches Verfahren zum Ausschluss etwaiger Befälle durch das Hodgkin-Lymphom. Auf eine Knochenmarkbiopsie kann daher bei Durchführung der [18F]FDG-PET regelhaft verzichtet werden

Influences on PET Quantification and Interpretation

Various factors have been identified that influence quantitative accuracy and image interpretation in positron emission tomography (PET). Through the continuous introduction of new PET technology—both imaging hardware and reconstruction software—into clinical care, we now find ourselves in a transition period in which traditional and new technologies coexist. The effects on the clinical value of PET imaging and its interpretation in routine clinical practice require careful reevaluation. In this review, we provide a comprehensive summary of important factors influencing quantification and interpretation with a focus on recent developments in PET technology. Finally, we discuss the relationship between quantitative accuracy and subjective image interpretation

Quantitative assessment of F-18-FDG PET in patients with Hodgkin lymphoma: is it significantly affected by contrast-enhanced computed tomography attenuation correction?

Objective The reliability of visual and quantitative response assessment may be impaired owing to inconsistent scanning protocols and image reconstruction methods of 2-deoxy-2-[F-18]fluoro-d-glucose (F-18-FDG) PET. Hence, this study investigates the effect of contrast-enhanced computed tomography (CT) attenuation correction in patients with Hodgkin lymphoma. Patients and methods In 10 consecutive patients undergoing either staging or response assessment, F-18-FDG PET images were attenuation-corrected once on the basis of unenhanced CT and additionally using contrast-enhanced CT. Reconstruction was performed in both cases with ordered subset expectation maximization (OSEM) and ultra-high definition (UHD) algorithm. While maximum and peak standardized uptake value (SUV) were obtained from tumour tissue (lesionSUV(max) and lesionSUV(peak)), maximum and mean SUVs were determined within the background regions liver (liverSUV(max) and liverSUV(mean)) and mediastinal blood pool (mbpSUV(max) and mbpSUV(mean)). Results After switching to contrast-enhanced CT attenuation correction, lesionSUV(max) and lesionSUV(peak) increased on average by 2.55 +/- 3.24 (P=0.018) and 3.64 +/- 3.22% (P=0.008), respectively, with OSEM and by 4.59 +/- 5.49 (P=0.005) and 3.84 +/- 5.65% (P=0.005), respectively, with UHD reconstruction. LiverSUV(max) and liverSUV(mean) showed a mean rise of 7.15 +/- 4.27 (P=0.005) and 6.97 +/- 2.18% (P=0.005), respectively, in the OSEM data sets and of 7.24 +/- 6.59 (P=0.017) and 6.29 +/- 2.83% (P=0.005), respectively, in the UHD images. The average increases of mbpSUV(max) and mbpSUV(mean) were 10.82 +/- 4.89 (P=0.005) and 12.40 +/- 3.73% (P=0.005), respectively, after OSEM, compared with 13.11 +/- 14.93 (P=0.005) and 11.50 +/- 12.19% (P=0.005), respectively, after UHD reconstruction. Conclusion As the use of CT contrast fluids results in a stronger SUV increase within the liver and mediastinal blood pool than within lymphoma tissue, this may have clinical consequences regarding visual and quantitative response assessment. Ideally, CT scans for PET attenuation correction should therefore be performed in the absence of a contrast agent

FDG-PET Imaging for Hodgkin and Diffuse Large B-Cell Lymphoma-An Updated Overview

Since the mid-1990s, F-18-fluorodeoxglucose (FDG)-positron emission tomography (PET) in combination with computed tomography has come to play a prominent role in the management of malignant lymphomas. One of the first PET applications in oncology was the detection of lymphoma manifestations at staging, where it has shown high sensitivity. Nowadays, this imaging modality is also used during treatment to evaluate the individual chemosensitivity and adapt further therapy accordingly. If the end-of-treatment PET is negative, irradiation in advanced-stage Hodgkin lymphoma patients can be safely omitted after highly effective chemotherapy. Thus far, lymphoma response assessment has mainly been performed using visual criteria, such as the Deauville five-point scale, which became the international standard in 2014. However, novel measures such as metabolic tumor volume or total lesion glycolysis have recently been recognized by several working groups and may further increase the diagnostic and prognostic value of FDG-PET in the future

Involved-Field Radiation Therapy Prevents Recurrences in the Early Stages of Hodgkin Lymphoma in PET-Negative Patients After ABVD Chemotherapy: Relapse Analysis of GHSG Phase 3 HD16 Trial

Purpose: The HD16 trial of the German Hodgkin Study Group (NCT00736320) demonstrated that radiation therapy in early stage Hodgkin lymphoma without risk factors cannot be safely omitted, and therefore combined modality therapy (CMT) remains the standard treatment. To demonstrate the local effect of consolidating involved-field radiation therapy (IF-RT), we performed an analysis of the recurrence pattern of positron emission tomography (PET)-negative HD16 patients. Methods and Materials: Between 2009 and 2015, 1150 patients with early-stage Hodgkin lymphoma without risk factors were randomly assigned to PET guided to 20 Gy IF-RT after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the HD16 study of the German Hodgkin Study Group. The study was designed as a prospective randomized controlled trial. We correlated the localization of recurrence with the panel-based IF-RT plan, which was drawn up for all patients prospectively, blinded to treatment allocation. Accordingly, we were able to identify recurrences that occurred at least in part inside or outside of the (potential) radiation field (in-field and out-field, respectively). Results: There were 328 and 300 PET-negative patients assigned to CMT and PET-guided treatment (ie, chemotherapy alone), respectively. Within a median 47-month follow-up, disease progression or recurrence was documented for 15 and 29 patients treated with and without IF-RT, respectively. Relapse localization was unknown in 1 CMT patient. Without IF-RT, 5-year inci-dence of in-field relapses was 10.5% (95% confidence interval, 6.5-14.6) compared with 2.4% (0.5-4.3) with CMT (P = .0008). There were no relevant differences in out-field recurrences (5-year incidence 4.1% [1.7-6.6] vs 6.6% [3.0-10.3], P = .54). There was no grade 4 toxicity observed during IF-RT, and incidence of second primary malignancies was similar in both groups. Conclusions: PET-negative patients of the HD16 study showed no significant toxicity after 20 Gy IF-RT, and we demon-strated that omission of IF-RT resulted in more, particularly local, recurrences. Therefore, consolidation IF-RT should still be considered as standard therapy in this setting. (C) 2021 Elsevier Inc. All rights reserved

Dual-Tracer PET/CT Protocol with [F-18]-FDG and [Ga-68]Ga-FAPI-46 for Cancer Imaging: A Proof of Concept

Imaging studieswithPET tracers acting as fibroblast activation protein inhibitors (FAPIs) show promising results that could usefully complement [F-18]-FDG in cancer imaging. Methods: All patients received [F-18]-FDG PET/CT and dual-tracer PET/CT after an additional injection of [Ga-68]Ga-FAPI-46 after the [F-18]-FDG PET/CT. Two readers visually compared detection rate and analyzed target-to-background ratios for tumor and metastatic tissue in single- and dual-tracer PET/CT. Results: Detection rate in dual-tracer PET/CT was visually as good as that in single-tracer PET/CT in 4 patients and superior in 2 patients, whereas target-to-background ratios were significantly higher in dualtracer PET/CT. Conclusion: Dual-tracer [F-18]-FDG/[Ga-68]Ga-FAPI-46 PET/CT within a single session is feasible and has potential. The dualtracer approach may have superior sensitivity to [F-18]-FDG PET/CT alone without compromising individual assessment of either scan

Outcome-based interpretation of early interim PET in advanced-stage Hodgkin lymphoma

The HD18 study for patients with newly diagnosed advanced-stage Hodgkin lymphoma (HL) used positron emission tomography (PET) after 2 cycles (PET-2) of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses (eBEACOPP) to guide further treatment. Here, we analyzed the impact of PET-2 results in the context of eBEACOPP according to the Deauville score (DS) in patients treated within the HD18 trial. Residual tissue was visually compared with reference regions according to DS. We analyzed the association between PET-2 uptake and baseline characteristics, progression-free survival (PFS), and overall survival (OS). One thousand five patients (52%) had DS1 or DS2, 471 (24%) had DS3, and 469 (24%) DS4. PET-2 uptake was associated with baseline risk factors large mediastinal mass, extranodal disease, and high International Prognostic Score (P<.0001 each). Among 722 patients receiving standard therapy with 6 cycles of eBEACOPP, 3-year PFS rates were 92.2%, 95.9%, and 87.6% with DS1-2, DS3, and DS4, respectively. Univariate hazard ratio (HR) for PFS in patients with DS4 vs DS1-3 was 2.3 (1.3-3.8; P=.002). DS4 was the only factor remaining significant for PFS in a multivariate analysis including the associated baseline risk factors. Three-year OS rates were 97.6% for DS1-2, 99.0% for DS3, and 96.8% for DS4, with a univariate HR for DS4 vs DS1-3 of 2.6 (1.0-6.6; P=.04). Residual uptake above that in the liver at PET-2 (ie, DS4) is an important risk factor regarding survival outcomes for patients treated with eBEACOPP upfront. We thus recommend DS4 as the cutoff value for PET-2 positivity. This trial was registered at www.clinicaltrials.gov as #NCT00515554