Background: PET-2 is widely adopted to select patients (pt) with advanced-stage cHL, who might benefit from intensifying or de-escalating therapy. Improved PFS has been reported in PET-2 positive pt switched from ABVD to escalated BEACOPP (eBEACOPP) compared to historical controls continuing ABVD. Nevertheless, pt with a PET-2 Deauville score (DS) 5 have a dismal prognosis, with PFS from 35% to 50% at 3 years despite treatment intensification.
Aim of Study: To refine outcome prediction, we conducted a pooled analysis of individual pt data from 3 multicenter trials: HD0607 GITIL/FIL, RATHL and SWOG S0816 focusing on pt with PET-2 DS 5 after ABVD who had intensified treatment with eBEACOPP or BEACOPP-14.
Methods: The prognostic value of clinical characteristics, laboratory parameters, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) at diagnosis was evaluated. MTV was calculated with an automatic software segmentation using SUV 4.0 threshold in each pt. Predictive factors of PFS measured from the date of PET-2 until progression, relapse, death from any cause or last follow-up, and overall survival (OS) were analyzed using Cox regression. Baseline characteristics and PET MTV/TLG of pt who failed vs those who achieved CR with intensified treatment were compared.
Results: Among 2231 pt with available PET scans for review, 136 (6%) PET-2 DS 5 pt were included in the study: M 72, F 64, median age 34 yrs, Nodular Sclerosis 71%, stage IIB/III/IV 29%/ 22% /49%, B symptoms 72%, IPS >3: 31%; bulky 22%; neutrophil/lymphocyte ratio > 6: 61%. At baseline median MTV and TLG were 243 cm3 (range, 1.6-4266) and 1476cm3 (range, 7.3-29386). After a median follow-up of 41 months, 3-yr PFS and OS were 32% (95% CI, 25-42) and 82% (95% CI, 75-89), respectively. In univariate analysis no clinical or laboratory parameter nor MTV was significantly associated with PFS, whereas age ≥ 45 years, median numbers of leukocytes, lymphocytes and monocytes were significantly associated with OS. Using a threshold of 192 cm3 for MTV calculated by Youden index, 3-year PFS and OS were 35% and 87% vs 34% and 79% for pt with low vs high MTV (p=ns).
Conclusions: Pt with PET-2 DS 5 after ABVD receiving intensified treatment have similar outcomes to refractory disease with only 32% 3-yr PFS. No factors measured at diagnosis were able to detect the later failures within the DS 5 cohort. Nevertheless, pt receiving PET-guided treatment intensification can benefit from a prolonged OS.
Simonetta Viviani, Chiara Pavoni, Sally F. Barrington, Luca Guerra, Heiko Schöder, Peter Johnson, Amy A. Kirkwood, Deborah M. Stephens, Jonathan W. Friedberg, Stephane Chauvie, Michael V. Knopp, Massimo Federico, Gunilla Enblad, Paolo Corradini, Andrea Gallamini, Alessandro Rambaldi, Corrado Tarella