PURPOSE In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007. PATIENTS AND METHODS Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate. Results Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy. For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, "B" symptoms, and nodular sclerosis histology were risk factors for inferior EFS. CONCLUSION With a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in EFS but no improvement in OS. For individual patients, the relative risks of relapse versus late effects of IFRT must be considered. Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT.
"After stratification for risk factors, a significant difference was evident for the low risk patients (89.1% vs. 100%, P=0.001), but not for the intermediate and high-risk groups (78.0% vs. 84% and 79.9% vs. 88.5%, respectively).18 Conversely, the GPOH-HD95 trial showed that the omission of RT was safe only for low-risk patients with complete response after chemotherapy (PFS of 96.8% versus 93.6%, p=0.42), whereas this strategy was not proven to be safe for the intermediate and the high risk groups (PFS 69.1% vs. 92.4%, "
[Show abstract][Hide abstract] ABSTRACT: Radiation therapy has a key role in the combined modality treatment of early-stage Hodgkin's Lymphoma (HL). Nevertheless, late toxicity still remains an issue. A modern approach in HL radiotherapy includes lower doses and smaller fields, together with the implementation of sophisticated and dedicated delivery techniques. Aim of the present review is to discuss the current role of radiotherapy and its potential future developments, with a focus on major clinical trials, technological advances and their repercussion in the clinical management of HL patients.
Mediterranean Journal of Hematology and Infectious Diseases 01/2014; 6(1):e2014035. DOI:10.4084/MJHID.2014.035
"Despite the relatively high overall survival for HL, the survivors are at risk of long-term complications and treatment-related mortality, especially pediatric, adolescent, and young adult patients. Recent trials in pediatric and adolescent HL have investigated chemotherapy regimens of varying dose intensities and reduction in radiotherapy usage based on risk group stratification.19–23 These approaches appeared to maintain the high response rate while reducing the burden of treatment. "
[Show abstract][Hide abstract] ABSTRACT: Despite the relative success of chemotherapy for Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD)30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody-drug conjugates (ADCs) appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE). It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two Phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA) granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies.
OncoTargets and Therapy 12/2013; 7:45-56. DOI:10.2147/OTT.S39107 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Late effects of treatment are an important cause of morbidity and mortality in childhood cancer survivors. The use of radiotherapy has been implicated as a risk factor for the development of many late complications. Several strategies have been employed in pediatric oncology to minimize the late effects of radiotherapy. These have included (1) omitting or delaying radiotherapy until the child is older, (2) decreasing radiotherapy doses and volumes by incorporating chemotherapy in the treatment regimen, (3) alteration of radiotherapy fractionation, (4) use of novel techniques to spare or minimize radiation dose to surrounding normal tissues, and (5) elimination of radiotherapy in favorable subsets of patients. In infants with brain tumors, delaying radiotherapy and giving chemotherapy until the child is 3 years old was a popular approach three to four decades ago with limited success with respect to tumor control. With the advent of modern radiotherapy technology, younger patients are now able to be treated with conformal techniques and reasonable neurotoxicity. Using chemotherapy to reduce doses of radiation therapy has been employed in standard-risk medulloblastoma, intracranial germinoma, Hodgkin lymphoma, and Wilms’ tumor. Likewise, the use of chemotherapy to reduce radiotherapy volumes has been employed in intracranial germinoma, Hodgkin lymphoma, and neuroblastoma and for the boost portion of treatments for rhabdomyosarcoma and Ewing sarcoma. There are a few phase III trials comparing conventional and hyperfractionated radiotherapy, but none of them have shown superiority of one over the other in terms of tumor control and late effects. Current protocols are testing the omission of radiotherapy in the most favorable subset of patients with Hodgkin lymphoma and Wilms’ tumor. Intensity-modulated radiation therapy is currently used in many children in developed nations. Proton therapy is available in a few centers; clinical results of treatment are accumulating regarding the effectiveness and long-term toxicity of this radiation modality.
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