Inter-Reader Reliability of Early FDG-PET/CT Response Assessment Using the Deauville Scale after 2 Cycles of Intensive Chemotherapy (OEPA) in Hodgkin's Lymphoma

Purpose The five point Deauville (D) scale is widely used to assess interim PET metabolic response to chemotherapy in Hodgkin lymphoma (HL) patients. An International Validation Study reported good concordance among reviewers in ABVD treated advanced stage HL patients for the binary discrimination between score D1,2,3 and score D4,5. Inter-reader reliability of the whole scale is not well characterised. Methods Five international expert readers scored 100 interim PET/CT scans from paediatric HL patients. Scans were acquired in 51 European hospitals after two courses of OEPA chemotherapy (according to the EuroNet-PHL-C1 study). Images were interpreted in direct comparison with staging PET/CTs. Results The probability that two random readers concord on the five point D score of a random case is only 42% (global kappa = 0.24). Aggregating to a three point scale D1,2 vs. D3 vs. D4,5 improves concordance to 60% (kappa = 0.34). Concordance if one of two readers assigns a given score is 70% for score D1,2 only 36% for score D3 and 64% for D4,5. Concordance for the binary decisions D1,2 vs. D3,4,5 is 67% and 86% for D1,2,3 vs D4,5 (kappa = 0.36 resp. 0.56). If one reader assigns D1,2,3 concordance probability is 92%, but only 64% if D4,5 is called. Discrepancies occur mainly in mediastinum, neck and skeleton. Conclusion Inter-reader reliability of the five point D-scale is poor in this interobserver analysis of paediatric patients who underwent OEPA. Inter-reader variability is maximal in cases assigned to D2 or D3. The binary distinction D1,2,3 versus D4,5 is the most reliable criterion for clinical decision making

FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?

To determine whether the current 18F-FDG PET response criterion for skeletal involvement in Hodgkin lymphoma (HL) is suitable, we performed a systematic evaluation of the different types of skeletal involvement and their response on PET after 2 cycles of chemotherapy (PET-2). A secondary objective was to observe the influence of the initial uptake intensity (measured as qPET) and initial metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: The initial PET scans of 1,068 pediatric HL patients from the EuroNet- PHL-C1 trial were evaluated for skeletal involvement by central review. Three types of skeletal lesions were distinguished: PET-only lesions (those detected on PET only), bone marrow (BM) lesions (as confirmed by MRI or BM biopsy), and bone lesions. qPET and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response for skeletal and nodal involvement on PET-2 were compared. Results: Of the 1,068 patients, 139 (13%) showed skeletal involvement (44 PET-only, 32 BM, and 63 bone). Of the 139 patients with skeletal involvement, 101 (73%) became PET-2–negative in the skeleton and 94 (68%) became PET-2–negative in the lymph nodes. The highest number of PET-2–negative scans in the skeleton was 42 (95%) in the 44 PET-only patients, followed by 22 skeletal lesions (69%) in the 32 BM patients and 37 (59%) in the 63 bone patients. Lesions that became PET-2–negative showed a lower initial median qPET (2.74) and MTV (2 cm3) than lesions that remained PET-2– positive (3.84 and 7 cm3, respectively). Conclusion: In this study with pediatric HL patients, the complete response rate for skeletal involvement on PET-2 was similar to that for nodal involvement. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion—comparison with the local skeletal background—is well suited. The initial qPET and MTV of skeletal lesions were predictive of the PET-2 result. Higher values for both parameters were associated with a worse PET-2 response

Frequency of Deauville (D) scores by reader R1 –R5.

<p>Frequency of Deauville (D) scores by reader R1 –R5.</p

Residual uptake in the mediastinum vs. thymus.

<p>Case 12: a) Lymphoma involvement of the upper and middle mediastinum including the thymus before treatment. b) and c) very slightly enhanced uptake as compared to the mediastinum after two cycles ChT. The interpretation might be complicated by the difficult decision whether this finding implies residual tumor uptake or physiological but inhomogeneous uptake in the thymus. Deauville score of the readers R1-5, respectively: 1-1-3-3-3. Courtesy Dept. Nuclear Medicine, Blackrock Clinic, Dublin, Ireland.</p

Discrepant D scoring of the mediastinum.

<p>Case 39: a) extensive lymphoma involvement of the left side of the upper mediastinum before treatment. b) residual mass after two cycles ChT. c) highest residual FDG uptake in the dorsal part of the residuum. D) It is difficult to decide if this highest FDG uptake is above or below the liver uptake. The interpretation is complicated by the small size of the hottest part of the residuum. Deauville score of the readers R1-5, respectively: 3-3-4-4-4. Courtesy M. Reinhardt, Dept. Nuclear Medicine, Pius-Hospital, Oldenburg, Germany.</p

Discrepant D scoring of the right supraclavicular region.

<p>Case 63. a) Tumour involvement before treatment. b) Residual mass in this region after two cycles of OEPA. c) and d) slightly enhanced FDG uptake above background in this area. Interpretation might be complicated by a slightly enhanced FDG uptake symmetrically in the left supraclavicular area which, however, is in the surrounding of a catheter and by the inhomogeneous uptake in the mediastinum. Deauville score of the readers R1-5, respectively: 1-1-3-1-2. Courtesy Dept. Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden.</p

Discrepancy analysis by region using the D1,2 vs D3 vs D4,5 three category scale.

<p>Discrepancy analysis by region using the D1,2 vs D3 vs D4,5 three category scale.</p

Agreement statistics for Deauville (D) scoring among five readers.

<p>Agreement statistics for Deauville (D) scoring among five readers.</p