Interim-PET Scan Interpretation In the Ongoing Prospective Clinical Trial HD 0607, In Advanced-Stage Hodgkin Lymphoma: Results of the the Expert Panel Review
Authors: Gallamini Andrea , Biggi Alberto , Chauvie Stephane , Stancu Alexandru , Fallanca Federico , Chiaravalloti Agostino , Gregianin Michele , Ficola Umberto , Guerra Ugo , Mennitto Maria Rosaria , Rambaldi Alessandro 
Published: October 2019

Abstract
Abstract 3891

Background:
several PET response-adapted prospective clinical trials are running at the moment, aimed at assessing the role of chemotherapy intensification in ABVD-treated Hodgkin Lymphoma (HL) patients with interim PET-positive after 2 cycles (PET-2). Standard interim-PET interpretation rules are still lacking, and expert review panels for PET interpretation have been implemented in these trials. We report here the results of PET-2 review in the HD 0607 trial.

Patients and methods:
starting from July 2008 till now, 236 advanced-stage HL patients have been consecutively enrolled in the Italian GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter clinical trial HD 0607 (NCT Identifier: NCT00795613). Advanced-stage (IIB-IVB) HL patients are first treated with 2 ABVD courses and PET-2 performed afterwards. All the non-negative PET-2 scan are reviewed by the expert panel. Non-negative PET-2 is defined as any scan with any residual FDG uptake outside the physiological areas of the tracer concentration. All the non-negative PET-2 according to the local centers (PET-2loc) are uploaded on the dedicated website (http://magic5.to.infn.it/gitil), along with the baseline scans. Six independent reviewers re-interpret the scans according to the 5-point semiquantitative score with mediastinum and liver as reference organs for residual fluorodeoxyglucose (FDG) uptake (Deauville score, Meignan 2009). The first three reviewers replying within 72 hours from PET upload determine the panel final decision; the remaining three report the scans later. Patients with a score 4 or 5 shifted to BEACOPP or Rituximab-BEACOPP escalated treatment; patients with score 1–3 continued with ABVD. Patient with bulky lesion (defined as a nodal mass with the largest diameter 3 6 cm) were treated with IF-RT.

Results:
199/236 patients performed a PET-2 scan: 131 (66%) showed a negative, 68 (33%) a non-negative scan. These 68 PET-2loc were reviewed (PET-2rev.); the clinical characteristics of patients with a reviewed and unreviewed PET-2loc were the following: mean age 32 vs.35, Stage III 19/68 (28%) and 61/131(46%), Stage IV 26/68 (39%) and 45/131 (34%), Bulky 44/68 (65%) and 93/131 (71%), IPS 3 or more 20/68 (29%) and 20/131 (15%), respectively. As a result of review there were 32 positive PET-2rev. and 36 negative PET-2rev. The median PET-2 review time from the uploading in the website to the third reviewer's report was 48 hours (1-90). The 32 positive PET-2rev scans showed a single residual focus in 28 and multiple foci of residual FDG uptake in 4 cases (all score 5). 22 showed a single lesion in the mediastinum, 4 in superficial lymph nodes and 2 in the lung. In 25/28 (89%) patients the single residual FDG uptake was within a bulky lesion and in 3/28 was outside it. The concordance rate among couples of reviewers for a positive vs. negative scan, measured with Cohen's Kappa, ranged between 0.76 (substantial agreement) and 0.92 (almost perfect agreement). The overall concordance rate measured with Krippendorf's Alpha, (assuming chance = 0 and perfect agreement =1) was 0.82. Lower concordance among reviewers was found in scans showing FDG residual uptake in anatomical structures not clearly related to lymphoma (brown fat, large vessels, bowel, tonsil, and inflammatory lung lesions).

Conclusions:
these data show that (1) the preliminary reports of a very high binary and overall concordance rate among reviewers using the Deauville score for PET-2 reporting (Barrington 2010) have been confirmed; (2) the online review process for PET-2 scan is feasible and simple; (3) most of the positive PET-2 scan showed a residual FDG uptake in the site of bulky disease, mostly in mediastinum.

Disclosures:
No relevant conflicts of interest to declare.