Prognostic impact of presentation phenotypes in early-stage favorable Hodgkin lymphoma

In early-stage favorable Hodgkin lymphoma (ES-HL), lymph node involvement patterns (NIP) have not been investigated until now. Adding finer granularity to the current disease classification system evaluated through systematically incorporating NIP alongside established clinical variables may help to identify distinct patient subgroups and improve the understanding of ES-HL.

A total of 3715 patients with ES-HL treated within the German Hodgkin Study Group HD10, HD13, and HD16 studies was retrospectively analyzed (stage I/II without risk factors). Involved lymph node regions were categorized into predefined anatomical areas, and the distribution patterns of affected lymph node regions were explored. Associations of patterns with baseline characteristics, histology, and 5-year progression-free survival (PFS) were analyzed using univariate and multivariable models.

Despite 22 possible combinations, 91.6% of patients presented with one of the six most common NIP. They differed in terms of age, sex distribution, weight, hemoglobin levels, and histologic subtype composition. For example, the combination of cervical and mediastinal involvement was more frequent in younger patients, females, enriched for nodular sclerosis histology, and associated with superior 5-year PFS compared to other patterns (95.1% vs 91.9%, p < .001). Conversely, the combination of cervical and axillary involvement was associated with decreased 5-year PFS (85.3% vs 93.4%, p < .001) and was enriched for male sex and nodular lymphocyte-predominant Hodgkin lymphoma.

Different presentation phenotypes exhibit distinct clinicopathologic characteristics and have prognostic impact in ES-HL. Further studies integrating molecular profiling are warranted to elucidate root mechanisms and possibly refine risk group allocation.