Long-term follow-up of patients treated with radiotherapy alone for early-stage histologically aggressive non-Hodgkin's lymphoma.
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ABSTRACT:
SUBMITTER: Spicer J
PROVIDER: S-EPMC2409646 | biostudies-other | 2004 Mar
REPOSITORIES: biostudies-other
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Project description:Chemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated with late treatment-related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths.We randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin's lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy. Patients in the ABVD-only group, both those with a favorable risk profile and those with an unfavorable risk profile, received four to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy, patients who had a favorable risk profile received subtotal nodal radiation therapy alone and patients with an unfavorable risk profile received two cycles of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year overall survival.The median length of follow-up was 11.3 years. At 12 years, the rate of overall survival was 94% among those receiving ABVD alone, as compared with 87% among those receiving subtotal nodal radiation therapy (hazard ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to 0.99; P=0.04); the rates of freedom from disease progression were 87% and 92% in the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI, 0.99 to 3.69; P=0.05); and the rates of event-free survival were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P=0.60). Among the patients randomly assigned to ABVD alone, 6 patients died from Hodgkin's lymphoma or an early treatment complication and 6 died from another cause; among those receiving radiation therapy, 4 deaths were related to Hodgkin's lymphoma or early toxic effects from the treatment and 20 were related to another cause.Among patients with Hodgkin's lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes. (Funded by the Canadian Cancer Society and the National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.).
| S-EPMC3932020 | biostudies-literature
Project description:Application of advances in genomic and proteomic technologies has provided molecular insights into distinct types of aggressive B- and T-cell non-Hodgkin's lymphomas (NHLs). This has led to the validation of novel biomarkers of classification, risk-stratification, and druggable targets. The promise of novel treatments from genomic research has been slow to materialize because of the lack of a therapeutic signature for the distinct NHL subtypes. Patients with lymphoma with aggressive disease urgently require the development of novel therapies on the basis of investigation of dysregulated intracellular oncogenic processes that arise during lymphomagenesis. Although monoclonal antibodies have made significant contributions to the armamentarium of B-cell NHL therapy (eg, anti-CD20), parallel development of small-molecule inhibitors (SMIs) to intracellular targets has lagged behind. Despite these deficiencies, several promising anti-NHL therapies are in development that target immune kinases of the B-cell receptor signaling pathway, mammalian target of rapamycin complex, proteasome, DNA/histone epigenetic complex, antiapoptosis, neoangiogenesis, and immune modulation. This review focuses on novel SMI therapeutic strategies that target overlapping core oncogenic pathways in the context of the 10 hallmarks of cancer. Furthermore, we have developed the concept of a therapeutic signature using the 10 hallmarks of cancer, which may be incorporated into novel phase I/II drug development programs.
| S-EPMC3138544 | biostudies-other
Project description:BackgroundThe efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era.MethodsWe treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival.ResultsOf 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P=0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P=0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P=0.04 for interaction) and overall survival (P=0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group.ConclusionsEarly autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation. (Funded by the National Cancer Institute, Department of Health and Human Services, and others; SWOG-9704 ClinicalTrials.gov number, NCT00004031.).
| S-EPMC3985418 | biostudies-literature
Project description:It is unknown whether breast cancer (BC) characteristics among young women treated with radiotherapy (RT) for Hodgkin's lymphoma (HL) differ from sporadic BC.Using population-based data, we calculated BC risk following HL according to clinicopathologic features.Compared with BC in the general population, risks of oestrogen receptor (ER)-positive/progesterone receptor (PR)-positive and ER-negative/PR-negative BC in young, irradiated HL survivors were increased five-fold (95% confidence interval (CI)=3.81-6.35) and nine-fold (95% CI=6.93-12.25), respectively. Among 15-year survivors, relative risk of ER-negative/PR-negative BC exceeded by two-fold (P=0.002) than that of ER-positive/PR-positive BC.Radiotherapy may disproportionately contribute to the development of BC with adverse prognostic features among young HL survivors.
| S-EPMC2965878 | biostudies-other
Project description:A reduced immune surveillance due to immune deficiency or treatment with immunosuppressive drugs is associated with a higher risk to develop aggressive Non-Hodgkin's lymphoma (NHL). Nevertheless, NHL also develops in immunocompetent patients indicating an escape from the immune system. T cell function in advanced aggressive lymphoma is not well characterized and the molecular mechanisms how malignant B cells influence T cell function are ill-defined. We therefore studied T cell function in E?-myc transgenic mice that develop an aggressive B cell lymphoma with some similarities to human Burkitt-lymphoma (BL). In advanced lymphoma, the number of T cells was severely reduced and the remaining CD4+ and CD8+ T cells lost the capacity to produce effector cytokines and expand upon re-stimulation. T cells in lymphoma-bearing mice were characterized by the expression of the immune inhibitory molecules programmed death (PD)-1, 2B4 and lymphocyte activation protein (LAG)-3. The proto-oncogene c-Myc not only drives cell proliferation and disease progression but also induces apoptosis of the malignant cells. We found that apoptotic lymphoma cells release purine metabolites that inhibit T cell function. Taken together, our data document that the characteristic high cell turnover and apoptotic rate in aggressive NHL induce a severe T cell dysfunction mediated by several immune-inhibitory mechanisms including ligation of inhibitory ligands and purine metabolites. Blocking a single mechanism only partially restored T cell function and did not increase survival of lymphoma mice.
| S-EPMC5739580 | biostudies-literature
Project description:Patients with advanced aggressive B-cell non-Hodgkin lymphomas (NHL) are usually treated with rituximab in combination with chemotherapy. However, disease relapse rates are high. Radiotherapy (RT) has been shown to be efficacious in treating early-stage NHL but its role in advanced stage diseases is unclear. We performed a systematic review of randomized controlled trials (RCTs) comparing chemotherapy with RT to chemotherapy alone in patients with newly diagnosed advanced aggressive NHL. We searched online databases and pooled similar outcome estimates. For time-to-event outcomes, we estimated hazard ratios (HR) for overall survival (OS) and event-free survival (EFS) using the fixed-effect model. Two RCTs involving 254 patients met inclusion criteria. The trials were single-centre RCTs with follow-up period of five and ten years. Both trials were conducted in the pre-rituximab era. Patients treated with consolidation RT had better OS (HR for mortality 0.61; 95 % CI 0.38 to 0.97) and EFS (HR for mortality 0.67; 95 % CI 0.46 to 0.98) compared to those who received no RT. There was an apparent benefit of RT on local control (OR 0.09; 95 % CI 0.04 to 0.20); although this was estimated as a dichotomous rather than time-to-event outcome. Limited evidence shows benefits of consolidation RT in advanced aggressive NHL. However, we were not able to estimate the effect size with confidence due to small number of trials and sample size. We cannot recommend routine consolidation RT in advanced aggressive NHL. More RCTs with the inclusion of rituximab and PET-CT monitoring are needed.
| S-EPMC5735338 | biostudies-literature
Project description:Sarcoidosis + Follow-up 6 month after Keywords = sarcoidosis Keywords = follow-up Keywords: other
2005-01-18 | GSE1907 | GEO
Project description:BACKGROUND:Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma. METHODS:We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival. RESULTS:At a median follow-up of 24.6 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95% CI, 0.45 to 1.18]; P=0.20) [corrected]. All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity. CONCLUSIONS:A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490 ; EudraCT number, 2011-005450-60 .).
| S-EPMC5819601 | biostudies-literature
Project description:We report corresponding gene expression, promoter methylation patterns of differential DHSs as well as differentially occupied TF binding motifs using surrounding DNAseI cut profiles. Overall, our study provides a framework for model studies of HL and NHL pathologies.
2014-09-24 | GSE51813 | GEO
Project description:BACKGROUND:Survivors of Hodgkin's lymphoma (HL) treated as adults are at risk for late effects of therapy. However, the burden of late morbidity and mortality among adults treated for HL remains incompletely characterized. METHODS:Vital status and, for deceased, cause of death were determined for 746 adults treated on a first-line trial at a single center from 1975 to 2000. Survivors completed a detailed survey describing their physical and mental health. A severity score (grades 1-4, ranging from mild to life-threatening or disabling) was assigned to self-reported conditions. RESULTS:At a median follow-up of 22 years, 227 of patients (30.4%) had died, 107 (47.1%) from HL, 120 (52.9%) from other causes, including second primary malignancies (SPMs) (n = 52) and cardiovascular disease (n = 27). Across the duration of follow-up, all-cause and SPM-specific risk of death remained higher than predicted by normative data. Among survivors, late morbidity survey data are available for 238 patients (45.9%). Ninety-four-point-one percent of respondents reported at least one morbidity, and 47.5% reported at least one grade 3 or 4 morbidity; 20.2% reported two or more grade 3 morbidities. Commonly reported morbidities included cardiovascular (54.6%), endocrine (68.5%), pulmonary disease (21.4%), and nonfatal second malignancy (23.1%). Anxiety, depression, and fear of recurrence were frequently reported. CONCLUSIONS:Among a large cohort of patients treated for HL with extensive follow-up, risk of late mortality from causes other than HL and prevalence of late medical morbidity are high. Guidelines for prevention, screening, and management of late effects in adult survivors of HL are needed.
| S-EPMC6281032 | biostudies-literature