Complete Remission on 18F-FDG-PET Prior to Autologous Stem Cell Transplantation Predicts Superior Event Free Survival of Patients with Relapsed or Refractory Hodgkin Lymphoma.
Authors: Peinert Stefan , Hoyt Rosemary , Szer Jeffrey , Seymour John F. , Prince H. Miles , Roberts Andrew W , Rigacci Luigi , Grigg Andrew , Ritchie David S. 
Published: April 2020

Abstract
In patients (pts) with Hodgkin lymphoma (HL) receiving first-line chemotherapy, interim restaging with 18F-FDG-PET scan (FDG-PET) after 1 or 2 cycles has been shown to predict event free survival (EFS) with high sensitivity and specificity overriding the clinical International Prognostic Score (IPS). The predictive value of FDG-PET in patients with relapsed or refractory HL undergoing high dose chemotherapy and autologous stem cell transplantation (ASCT) is less well established. Previous studies have either included functional imaging with both gallium and FDG-PET scans or performed analyses of Hodgkin and non-Hodgkin lymphoma as a combined cohort. Our aim was to determine the predictive value of FDG-PET in pts with HL planned to receive ASCT. A retrospective analysis was undertaken of 52 consecutive pts treated at three centres. Pts with primary refractory (n=25) or relapsed HL (n=27) underwent FDG-PET scanning after salvage chemotherapy and before ASCT. Remission status by FDG-PET post salvage, treatment details, including salvage type and peri-transplant involved field radiotherapy (IFRT), and clinical characteristics were recorded and EFS and overall survival (OS) post ASCT were evaluated. Survival analyses were performed using Kaplan-Meier estimates and cohorts were compared using the Log-rank (Mantel-Cox) and the Gehan-Breslow-Wilcoxon Test. The contingency of data between different groups was analysed using Fisher’s exact test. The median age of pts at the time of ASCT was 38 [18–61] years, 27/52 (52%) were male. The majority of pts received salvage chemotherapy with VIC (etoposide 100mg/m2 day (d)1-3, ifosfamide 5g/m2 d2, carboplatin AUC 5), n=24) or MADEC (methotrexate 400mg/m2 d1, cytosine arabinoside 75mg/m2 d1-5, dexamethasone 40mg d1-4, etoposide 75mg/m2 d1-5, cyclophosphamide 750mg/m2 d2, n=13), other chemotherapy regimens used were BEACOPP, n=3, IGEV, n=3, FGIV, n=2, DHAC, n=2 or others, n=1 each. After salvage, 23/52 (44%) of pts were FDG-PET-negative and 29/52 (56%) were positive. With a median follow-up of 30 [4–115] months in surviving pts, the 6-year actuarial rates for EFS and OS for FDG-PET negative versus FDG-PET positive pts were 73% and 34% (p=0.03), and 95% and 64%, respectively (p=0.06). Overall, the addition of peri-transplant IFRT did not impact on EFS or OS. However, in 13 pts with post salvage FDG-PET-avid disease which was limited to an area entirely encompassed by IFRT, actuarial rates of 6-year EFS and OS were 51% and 66% and therefore not significantly different from those obtained in FDG-PET-negative pts (p=0.47 and 0.39, respectively). Female gender was the only factor predictive for obtaining a complete FDG-PET-remission post salvage therapy (p=0.011). Female gender and duration of first remission of ≥ 12 months also independently predicted for superior EFS (p=0.017 and 0.039), respectively. Other characteristics including the presence of B-symptoms, extra-nodal disease prior to salvage, age ≥ 38 years, type of salvage or conditioning regimen used, or transplant centre did not influence EFS or OS. Our data show that FDG-PET-status after salvage chemotherapy for relapsed or refractory HL is a powerful predictor of EFS after ASCT demonstrating an excellent outcome for FDG-PET-negative pts. In pts with limited FDG-PET-avid disease following salvage chemotherapy, the addition of IFRT may reduce the poor prognostic impact of residual FDG-PET positivity in a subset of patients.