Relative Reduction of Residual Tumor Improves Outcome Prediction of PET After Effective Chemotherapy for Patients with Advanced Stage Hodgkin Lymphoma
Authors: Engert Andreas , Kobe Carsten , Haverkamp Heinz , Kuhnert Georg , Markova Jana , Lohri Andreas , Klutmann Susanne , Amthauer Holger , Diehl Volker , Borchmann Peter , Dietlein Markus 
Published: October 2019

Abstract
Abstract 3684

Purpose:
Positron emission tomography (PET) is being established as a valuable marker to guide the use of additional radiotherapy (RT) after effective chemotherapy in patients with advanced stage Hodgkin Lymphoma (HL). The present analysis compares the prognostic impact of PET with conventional imaging methods (CIM).

Methods:
A prospective cohort of 739 patients with advanced stage HL treated within the GHSG HD15 trial who achieved at least partial remission and presented with persistent mass ≥2.5 cm after 6–8 cycles of BEACOPP chemotherapy underwent PET scanning at one of 37 participating GHSG PET centers. A central multidisciplinary panel consisting of experts from medical oncology, radiology, radiation oncology, and nuclear medicine reviewed PET and CT scans as well as available conventional X-rays. This panel decided on the need of additional radiotherapy (30Gy to residual masses) if PET was positive according to standard criteria, or no further treatment if PET was negative. Prognosis was evaluated using progression free survival (PFS) measured from the panel decision; groups were compared using the log rank test. Potential prognostic factors were investigated using ROC analysis and logistic regression. The latter analysis included 710 patients with progression, relapse or at least one year of follow-up after PET review without tumor recurrence.

Findings:
The 548 PET negative of 739 patients (74%) had a 4-year PFS of 91.5%. In contrast, the 191 PET positive patients (26%) had a 4-year PFS of 86.1% (p=0.022). Compared to PET, CIM would have resulted in a different treatment recommendation for 28% of patients. CIM was unable to separate patients by risk of recurrence, both, for all patients and in PET negative or PET positive subgroups. Concordance between local and central review was observed in 90% of cases with only 3 recurrences so far in the 10% (n=71) discordant patients. Half of the discordant patients (n=36) were judged PET positive by central review and accordingly had additional radiotherapy. When investigating other potential indicators of response, ROC analysis showed that only the relative reduction of residual tumors was significantly associated with outcome (AUC 0.65, 95% CI 0.57 to 0.73), while other factors such as the largest diameter of the residual tumor at initial staging or restaging as well as IPS were not. When the 54 PET positive patients who had a tumor reduction of less than or equal to 40% were compared to those 135 PET positive patients having a tumor reduction of more than 40%, the OR for recurrence within a year was 5.6 (95% CI 2.1 to 15.2). However, even in this high-risk group, most of the patients did not relapse: the 4-year PFS was 72.8% and most events occurred in the first year after PET review. The low risk group had a 4-year PFS comparable to the rate of PET negative patients (92%). However, 94% of these patients were irradiated, while more than 98% of PET negative patients were not. Both PET negative groups had favorable 4-year rates of 89.4 (≤ 40% reduction) and 92.4% (more than 40% reduction).

Conclusion:
The rate of concordance between local and central PET review in the present analysis was 90%. While morphological imaging alone did not sufficiently predict PFS, the magnitude of tumor shrinkage may help to identify those PET positive patients at higher risk for progression or relapse despite additional radiotherapy. Since the risk for relapse is highest in the first year after treatment, maintenance treatment should be discussed for this rather small group of patients.

Disclosures:
Engert: Takeda, Millennium: Honoraria, Research Funding. Borchmann:Millenium The Takeda Oncology Company: Research Funding; Takeda Pharma GmbH: Travel Grants, Travel Grants Other.