Prognostic value of lesion dissemination in doxorubicin, bleomycin, vinblastine, and dacarbazine‐treated, interimPET‐negative classical Hodgkin Lymphoma patients: A radio‐genomic study

Abstract

We evaluated the prognostic role of the largest distance between two lesions (Dmax), defined by positron emission tomography (PET) in a retrospective cohort of newly diagnosed classical Hodgkin Lymphoma (cHL) patients. We also explored the molecular bases underlying Dmax through a gene expression analysis of diagnostic biopsies. We included patients diagnosed with cHL from 2007 to 2020, initially treated with ABVD, with available baseline PET for review, and with at least two FDG avid lesions. Patients with available RNA from diagnostic biopsy were eligible for gene expression analysis. Dmax was deduced from the three‐dimensional coordinates of the baseline metabolic tumor volume (MTV) and its effect on progression free survival (PFS) was evaluated. Gene expression profiles were correlated with Dmax and analyzed using CIBERSORTx algorithm to perform deconvolution. The study was conducted on 155 eligible cHL patients. Using its median value of 20 cm, Dmax was the only variable independently associated with PFS (HR = 2.70, 95% CI 1.1–6.63, pValue = 0.03) in multivariate analysis of PFS for all patients and for those with early complete metabolic response (iPET‐). Among patients with iPET‐low Dmax was associated with a 4‐year PFS of 90% (95% CI 82.0–98.9) significantly better compared to high Dmax (4‐year PFS 72.4%, 95% CI 61.9–84.6). From the analysis of gene expression profiles differences in Dmax were mostly associated with variations in the expression of microenvironmental components. In conclusion our results support tumor dissemination measured through Dmax as novel prognostic factor for cHL patients treated with ABVD.

Combination of baseline PET/CT total metabolic tumor volume, lesion dissemination and TP53 mutations predicts rapid progression of diffuse large B-cell lymphoma

“…Dmax has been demonstrated to identify poor prognosis in patients with DLBCL, Hodgkin lymphoma or other lymphomas [29][30][31] , as a 3D feature simple to calculate with an intuitive interpretation. Although Dmax was less affected by height during the LNH073B study [29] , we think it is more reasonable to use body surface area to standardize Dmax, considering the consistency of comparison.…”

Dmax: A simple and reliable PET/CT‐derived new biomarker of lymphoma outcome?

“…The study published by Durmo et al 15 . tested the capacity of D max to predict treatment outcome in a retrospective cohort of patients with classical HL treated with ABVD regimen confirming the prognostic role of this biomarker in this type of lymphoma.…”

“…Their combination with MTV in predictive models showed a significant improvement of the prognostic value of the only tumor burden estimation (by MTV). [12][13][14] The study published by Durmo et al 15 tested the capacity of D max to predict treatment outcome in a retrospective cohort of patients with classical HL treated with ABVD regimen confirming the prognostic role of this biomarker in this type of lymphoma. In a multivariate analysis including the most common clinical parameters and baseline PET metrics (MTV, TLG and SUVmax), D max resulted the only independent predictor of PFS.…”

“…However, regardless of its prognostic superiority as an individual parameter over volume-based PET metrics, some recent studies demonstrated -in both HL and non-HL lymphoma cohortsthat combining D max with texture features or clinical characteristics may lead to better predictive models compared to the only MTV. 13, [16][17][18] Moreover, Durmo et al 15 reported a maintained high predictive value of D max when combined with interim PET (iPET) results. In particular a high D max value identified a subgroup of patients with negative iPET (i.e., Deauville score 1-3 after 2 cycles of therapy), who despite the early metabolic remission have an increased risk of relapse.…”

“…Moreover, Durmo et al 15 . reported a maintained high predictive value of D max when combined with interim PET (iPET) results.…”