Tumour burden predicts treatment resistance in patients with early unfavourable or advanced stage Hodgkin lymphoma treated with ABVD and radiotherapy

Abstract

The purpose of the work was to investigate the factors predicting early resistance to treatment in Hodgkin lymphoma. Many staging parameters, including relative tumour burden (rTB), were analysed in 246 patients with Hodgkin lymphoma in relation to early failure, that is, less than complete remission (i.e. partial response, null response or progression) or occurrence of early relapse, as clinical expressions of resistance to treatment. Patients with early unfavourable disease were 129 and were treated with four to six cycles of ABVD + involved field radiotherapy; 117 patients with advanced stage disease received six cycles of ABVD + optional irradiation to no more than two sites. The rTB was volumetrically measured through the evaluation of staging computed tomography for all the lesions except bone marrow involvement, which was quantified by calculation. The relationship with early resistance was analysed with logistic regressions. The rTB demonstrated to be the best predictor of early failure in both patient subsets, being superior to the multiparameter International Prognostic Score. The rTB showed a significant exponential relationship with the relative risk of early failure, and with inclusion of the extranodal involvement into the model, a single equation became adequate to predict resistance in both early unfavourable and advanced stage patients. The conclusions are that the rTB is the best pretreatment factor related to the risk of resistance to combined ABVD + radiotherapy and that this relationship can be mathematically expressed in an easy way. A simplified assessment of rTB is highly desirable.

Tumour burden at diagnosis as the main clinical predictor of cell resistance in patients with early stage, favourable Hodgkin lymphoma treated with VBM chemotherapy plus radiotherapy

“…These authors found that the majority of the known conventional prognostic factor are vague and inaccurate surrogates for TB, and likely, this is the reason for their prognostic value . Here, as previously demonstrated in patients with early unfavourable and advanced‐stage disease , the rTB was shown to be the best prognosticator of treatment resistance also in the present subset of patients characterized by limited involvement and favourable clinical presentation, who were treated with low‐intensity combination therapy. The limited number of patients evaluated and the retrospective basis of the study seem to have been counterbalanced by the clear‐cut evidence of the results.…”

“…Because it has been demonstrated that there is a good relationship between initial tumour burden (TB) and resistance to treatment in Hodgkin lymphoma—the current main obstacle to the cure of the disease —we planned to measure the initial TB in patients treated with VBM plus radiotherapy to verify whether this parameter retains a primary prognostic value also in this subset of patients with favourable disease features, treated with low‐intensity therapy, and to determine whether the parameter is able to predict the few early treatment failures. We hypothesized that in the case of satisfactory relationship, distinct limits of TB could be established which could predict both optimal efficacy of the combination therapy and an unacceptable risk of early treatment failure.…”

Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma - results of the UK HD3 relapse treatment strategy

“…It was interesting to note that patients who had stage IV at diagnosis were more likely to relapse with stage IV disease even if they had a complete or very good partial response (VGPR) at the end of primary treatment. Plainly, disease burden at diagnosis is a critical predictor of treatment resistance in patients with advanced stage HL (Dieckmann et al, 2003;Gobbi et al, 2012) and is the most plausible reason for this observation in our cohort.…”

Prognostic Factors in Hodgkin Lymphoma

“…Since measurement of bulk is limited to the single largest mass, it could underestimate the total tumor burden in patients with diffuse disease. Newer methods to measure tumor burden with CT volume or metabolic tumor volume may give more precise estimation of the tumor volume 5–7. Normalization of the tumor mass to the body surface (the relative tumor burden) yields a parameter with a reliable prediction for tumor control modulated by the use of chemotherapy regimens with different intensity 7.…”