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The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas.

ABSTRACT: Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin's lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-containing regimens. The incorporation of anthracycline-containing regimens was associated with improved progression-free survival (PFS) and overall survival (OS). Patients treated with nonanthracycline-containing regimens were more likely to have high-risk features and were less likely to undergo high-dose therapy and stem cell transplantation. However, anthracycline use remained an independent predictor of improved PFS and OS when adjusting for these confounding variables. Anthracycline-based regimens and consolidation with high-dose therapy and autologous stem cell transplantation in appropriately selected patients remains a viable option for patients unable to participate in a clinical trial. Long-term disease-free survival is not optimal, highlighting the need for an improved understanding of disease pathogenesis, and the development of novel therapeutic strategies.

SUBMITTER: Briski R

PROVIDER: S-EPMC4042304 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas.

Briski R R Feldman A L AL Bailey N G NG Lim M S MS Ristow K K Habermann T M TM Macon W R WR Inwards D J DJ Colgan J P JP Nowakowski G S GS Kaminski M S MS Witzig T E TE Ansell S M SM Wilcox R A RA

Blood cancer journal 20140530

Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin's lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-conta ...[more]

PMID: 24879115

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Project description:Background: The clinical course of relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) is variable, with limited efficacy data of second-line treatment in a post-rituximab real-world context. Hence, we explored the predictors and constructed a nomogram for risk stratification in this population. Patients and methods: Among 296 r/r DLBCL patients pretreated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) at the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between 2006 and 2017, 231 were included for nomogram construction. After randomization, we constructed the prognostic nomogram in the primary cohort (n=161) based on a multivariate analysis and confirmed it in the validation cohort (n=70). Additionally, we explored predictive factors for second-line therapy using a ordinal regression analysis. Results: Four independent prognostic factors including rituximab in the second-line setting, initial Eastern Cooperative Oncology Group (ECOG) performance status (PS), response to front-line treatment, and invasion on progression/recurrence were used to construct the nomogram. The nomogram had a C index of 0.70 with AUC values of 0.73 and 0.71 for the primary and validation cohorts, respectively. Subsequently, three risk groups (low, intermediate, and high) were determined with median overall survival (OS) of 38.0, 25.0, and 7.0 months, respectively. Additionally, we conducted a multivariate ordinal regression analysis and identified prior response to front-line treatment (odds ratio=4.50, 95% CI: 1.84-11.27, p=0.001) and bulky disease at diagnosis (odds ratio=0.36, 95% CI: 0.182-0.702, p=0.003) were two independent factors for second-line treatment efficacy. Conclusions: The established predictors for treatment efficacy and the novel nomogram for survival in r/r DLBCL patients could potentially be applied for risk stratification and treatment guidance in the post-rituximab era.

Project description:BackgroundAnthracycline-containing chemotherapy (Anth-C) is associated with long-term cardiovascular mortality. Although cardiovascular risk assessment has traditionally focused on the heart, evidence has demonstrated that vascular dysfunction also occurs during and up to 1 year following Anth-C. Whether vascular dysfunction persists long-term or negatively influences cardiac function remains unknown. Hence, the present study evaluated ventricular-arterial coupling, in concert with measures of vascular structure and function, in the years following Anth-C.MethodsArterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were measured during rest and exercise using echocardiography. Resting vascular function (flow-mediated dilation) and structure (carotid intima-media thickness, arterial stiffness) were also measured.ResultsThirty breast cancer survivors (6.5 ± 3.6 years after Anth-C) with normal left ventricular ejection fraction (LVEF) (60% ± 6%) and 30 matched controls were studied. At rest, no differences were found in Ea, Ees, Ea/Ees, or LVEF between groups. The normal exercise-induced increase in Ees was attenuated in survivors at 50% and 75% of maximal workload (p < .01). Ea/Ees was also higher at all workloads in the survivors compared with the controls (p < .01). No differences in vascular structure and function were observed between the two groups (p > .05).ConclusionIn the years after Anth-C, ventricular-arterial coupling was significantly attenuated during exercise, primarily owing to decreased LV contractility (indicated by a reduced Ees). This subclinical dysfunction appears to be isolated to the heart, as no differences in Ea were observed. The previously reported adverse effects of Anth-C on the vasculature appear to not persist in the years after treatment, as vascular structure and function were comparable to controls.Implications for practiceAnthracycline-induced cardiotoxicity results in significantly impaired ventricular-arterial coupling in the years following chemotherapy, owing specifically to decreased left ventricular contractility. This subclinical dysfunction was identified only under exercise stress. A comprehensive evaluation of vascular structure and function yielded no differences between those treated with anthracyclines and controls. Combined with a stress stimulus, ventricular-arterial coupling might hold significant value beyond characterization of integrative cardiovascular function, in particular as a part of a risk-stratification strategy after anthracycline-containing chemotherapy. Although vascular function and structure were not different in this cohort, this does not undermine the importance of identifying vascular (dys)function in this population, because increases in net arterial load during exercise might amplify the effect of reductions in contractility on cardiovascular function after anthracycline-containing chemotherapy.

Dataset Information

The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas.

Publications

The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas.

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