Health-related quality of life in patients with aggressive non-Hodgkin lymphoma: results from the PETAL trial

Abstract

When different therapies provide similar cure rates, health-related quality of life (HRQoL) may become crucial for the choice of treatment. In the Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas (PETAL) trial, we compared six cycles of R-CHOP with or without two extra doses of rituximab in prognostically favorable interim PET (iPET)-negative patients, while eight cycles of R-CHOP were compared with two R-CHOP cycles followed by six cycles of a more intensive protocol in prognostically unfavorable iPET-positive patients. As reported previously, treatment intensification did not improve outcome. HRQoL was assessed using the EORTC QLQ-C30 questionnaire. Pretreatment questionnaires were obtained from 558 out of the 862 participants (64.7%). Pretreatment HRQoL was significantly worse than in the general population. It was associated with age, gender, B symptoms, International Prognostic Index (IPI) and total metabolic tumor volume (TMTV). Physical and cognitive functioning predicted survival independent of IPI or TMTV. During treatment, some domains remained stable (e.g., cognitive functioning, nausea/vomiting), while others improved (e.g., emotional functioning, pain) or deteriorated (e.g., physical functioning, role functioning, fatigue). At the end of treatment, HRQoL was better in patients with controlled disease than in patients with progressive disease and better for iPET-negative patients than for iPET-positive patients. During follow-up, all HRQoL domains returned to levels similar to those reported for the general population. Differences between randomized treatment arms were not observed. The longitudinal data need to be interpreted with caution, because decreasing participation resulted in a selection of patients with increasingly good outcomes. ClinicalTrials.gov no. NCT00554164 (registered 11/5/2007).

Keywords: Aggressive non-Hodgkin lymphoma; Chemotherapy; Diffuse large B-cell lymphoma; Positron emission tomography; Quality of life.

Fig. 1

Global quality of life (left) and fatigue (right) at the pretreatment quality-of-life assessment in relation to the International Prognostic Index (top) or ascending quartiles of the total metabolic tumor volume (bottom). Cf. Table 2 for numbers of patients; p, Kruskal–Wallis test

Fig. 2

Progression-free survival (top) and overall survival (bottom) in relation to physical (left) or cognitive functioning (right) at the pretreatment quality-of-life assessment. Low, patients with scores below or equal to the median of all observed scores; high, patients with scores above the median. HR, hazard ratio; CI, confidence interval; p, log-rank test (cf. text for HR, CI and p adjusted for the covariates lymphoma subtype and International Prognostic Index)

Fig. 3

Four patterns of quality-of-life changes during treatment and follow-up. Top left, no change; top right, rapid improvement; bottom left, delayed improvement; bottom right, initial deterioration with subsequent improvement. Higher scores denote better performance. Cf. Table 3 for numbers of patients; iPET, interim positron emission tomography (before treatment cycle 3); EoT, 3–6 weeks after the end of treatment; 3-m, 6-m, 9-m and 12-m FU, 3-, 6-, 9- and 12-month follow-up; p, Kruskal–Wallis test

Fig. 4

Functioning (top) and symptoms (bottom) at the end-of-treatment (EoT) quality-of-life assessment in relation to the interim PET response. Negative interim PET response, 299 patients; positive interim PET response, 28 patients. Note that higher scores denote better performance in the functional scales, while higher scores represent worse performance in the symptom scales. p, Kruskal–Wallis test

Fig. 5

Progression-free survival in relation to completion versus non-completion of the quality-of-life questionnaire before treatment (top), at end of treatment (middle) and after 12 months of follow-up (bottom). Left, interim PET negative patients (good prognosis); right, interim PET positive patients (poor prognosis). HR, hazard ratio; CI, confidence interval; p, log-rank test