Shunan Qi1,2, Sarah Milgrom3, Bouthaina Dabaja,3, Richard Tsang4, Mario Levis5, Umberto Ricardi5, Eldad J. Dann6, Rebecca Lopez-Alonso, Andrea Ng7, Joachim Yahalom1
1 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 2 Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 3 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, 4 Department of Radiation Oncology and Biostatistics, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada, 5 Department of Oncology, Radiation Oncology, University of Torino, Torino, Italy, 6 Department of Hematology and Bone Marrow Transplantation, Rambam Medical Center, Haifa, Israel, 7 Department of Radiation Oncology, Brigham and Women‘s Hospital, Boston, MA, USA
Purpose: Controversy exists regarding the definition and prognostic significance of bulk in advanced-stage Hodgkin lymphoma (ASHL); bulk location (mediastinum vs. other sites) maybe also of relevance. This retrospective, multi-institutional study aimed to evaluate the significance of bulk in ASHL.
Patients and methods: The complete study cohort comprised 814 ASHL (stage III/IV) patients, divided into an exploratory cohort of 683 patients treated at 5 centers between 2000 to 2010 and a validation cohort of 131 patients treated at a 6th center. Endpoints of interest included progression-free survival (PFS) and overall survival (OS). Covariates included the greatest transverse diameter of the largest mass and the site of bulky disease. SmoothHR and Kaplan-Meier analyses were used to assess for an association of PFS and OS with covariates.
Results: In the exploratory cohort (n = 683), 533 patients (78%) received chemotherapy alone. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 78% of cases). Based on SmoothHR analysis, Maximum diameter had no association with PFS and a complex, U-shaped association with all-cause mortality (Fig 1A). Using 5 cm as a cut-off for bulk, Kaplan-Meier analyses confirmed the smoothHR results, with no significant difference in PFS between the two groups and significantly better OS in the group with bulk ≥5 cm (figure 1B). The site of bulk was incorporated to divide patients into 2 groups: Mediastinal Bulk (MB)-type, defined by the presence of bulky mediastinal disease (≥5 cm) with/without bulk at another site, and Non-Bulky/Non-Mediastinal Bulk (NB/NMB)-type. The MB-type had more favorable characteristics than the NB/NMB-type, including younger age, more frequent nodular sclerosis (NS) histology, and less frequent bone marrow involvement (P < 0.001, Fig 1C). The MB-type was associated with better OS than the NB/NMB-type on univariable analysis (5-year OS 92% vs. 86%, Fig 1D; hazard ratio, 0.53; 95% CI, 0.34 to 0.84; P = 0.007). These findings persisted in the subgroup treated with chemotherapy alone and were confirmed in an independent validation cohort.
Conclusion: In ASHL, maximum tumor diameter showed no significant association with PFS, but a complex association with OS reflected by a U-shaped logarithmic HR curve. Mediastinal bulk was associated with more favorable disease characteristics and improved OS. Mediastinal bulk in ASHL may be a surrogate of a more favorable biology.