A Prospective Ukrainian Multicentre Cohort Study of Pet Value Prognostic Role in Primary Patients with Hodgkin Lymphoma (HL): Six-Year a Brief Review
Authors: Novosad Olga , Kryachok Iryna , Gorbach Olexandr , Rudiuk Tymur , Pastushenko Ian , Kmetyuk Yaroslav , Karpova Olga , Mykhalska Larisa , Kozlov Viktor , Novikov Mykola , Oliinichenko Olena , Stratienko Viktoriya , Karnabeda Oksana , Ashykhmin Andrey , Kadnikova Tatyana , Shudrak Natalia 
Published: December 2023

Introduction : The PET-adapted approach for the treatment of patients with Hodgkin's lymphoma has long been used around the world. In Ukraine, this method has recently become actively used at all stages of treatment, which allows it to meet modern standards.

Airms. The primary endpoint was to assess the effectiveness of individualized approaches as a correlation between PET findings and response to therapy, type of regimen and clinical outcome (Event free (EFS) and overall survival (OS)). The second endpoint was to evaluate the impact of risk factors on the survival.

Methods. Of 278 evaluable patients, 64% were female; median age 43 years (range, 17-69 years). Patients received a treatment with ABVD or ABVD/AVD (more than 50% pts); BEACOPP-14/esc or “switched-regimens” (ABVD+BEACOPP-esc/14, BEACOPP-esc/14+ABVD). Metabolic PET imaging was performed to routine protocols using Deauville criteria for response assessment.

Results. Bulky disease (&gt;10 cm in any dimension) were presented in 74/278 (26.6%) of pts, B symptoms - in 126/278 (45.3%) and extranodal disease had 57/278 (20.5%).

93.8% of patients achieved remission (CR/PR) during the follow-up period (median timeline: 27 months). The ORR for patients with stage I-II was 87.2% (137/157) vs 80.1% (97/121) for patients with stage III-IV. We recorded a disease progression in 44 (15.8%) patients during and after the 1st line therapy, (median time to relapse - 8 months). Only 6 pts died due to HL.

In the study group, PET was performed at the beginning of treatment in 150 pts, interim in 248 and at the end of treatment in 190 pts. We found a trend in improved outcome after treatment in patients with at least two follow-up PETs (interim and EOT), indicating the effectiveness of individualized PET-adapted therapy.

Interim PET-CT was assessed as DS 1-2 in 127 patients (48.4%), DS 3 in 88 (33.6%), DS 4-5 in 47 pts (17.9%). In total, the disease progression occurred in 48.3% (15/31) of interim PET-positive (PET2+) patients and 11.5% (20/174) of interim PET-negative (PET2-) patients (p&lt;0.05).

After 6 year of follow-up EFS decreased in patients with PET2+ by 10% than the previously reported (PET2- pts 85% and vs 44% PET2+ pts, p=0.0001). Perhaps, despite the achievement of a partial metabolic response (DS-4), patients in this group still require intensification of treatment. Intermediate-risk group cohort (2B stage) to improve the EFS levels when the regimens was given BEACOPP-esc/14+ABVD vs ABVD+BEACOPP-esc/14 vs ABVD (80% vs 60% vs 55% respectively, p=0.03) and was independent of PET2 status. Also, a more intensified treatment for patients with stage III-IV of HL showed a significantly better level of EFS compared to the ABVD regimen, and it did not depend on PET2 status (Log-rank test, p=0.0003).

OS is the most patient-relevant outcome in oncology; large sample sizes and extended follow-up durations are needed to detect statistically significant differences in OS. After a median follow up of 70 months, the study met its primary endpoint in the PET-2 negative cohort, with 6-year OS of 97% versus 60% (p=0.004).

Interestingly, we did not find any correlation between EFS between risk groups 2B+bulky vs 2B without bulky (p=0.9) and also 2A+ (vs) - bulky (p=0.2). But we confirmed OS higher in pts with stage 2A vs 2B (98% vs 75%, respectively, p=0.03).

Conclusions . The results of the use of PET in patients with primary HL showed a high predictive value of PET, which affects event-free and overall survival.