Two Cycles of ABVD Followed by Involved Field Radiotherapy with 20 Gray (Gy) Is the New Standard of Care in the Treatment of Patients with Early-Stage Hodgkin Lymphoma: Final Analysis of the Randomized German Hodgkin Study Group (GHSG) HD10. Study Supported by the Deutsche Krebshilfe and in Part by the Competence Network Malignant Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 716-716 ◽  
Author(s):  
Andreas Engert ◽  
Volker Diehl ◽  
Annette Pluetschow ◽  
Hans T. Eich ◽  
Richard Herrmann ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Final Analysis ◽  
Standard Of Care ◽  
Combined Modality Treatment ◽  
Who Grade ◽  
Significant Difference ◽  
Involved Field ◽  
Involved Field Radiotherapy

Abstract Abstract 716 Background: There has been an ongoing debate on the best treatment for patients with early favourable Hodgkin lymphoma (HL). Open questions include the choice between combined modality treatment or chemotherapy only, the number of chemotherapy cycles needed and the optimal radiation dose. The GHSG thus conducted a randomized study for patients with early-stage favourable Hodgkin lymphoma (HD10) in which these questions were addressed. Methods: HD10 was an international prospectively randomized multicenter trial comparing 2 and 4 cycles of ABVD as well as 20Gy or 30Gy involved field radiotherapy (IFRT) in a 2 × 2 statistical design. Between 5/1998 and 1/2003, a total of 1370 patients from 329 centers were randomized into four arms: 4 × ABVD + 30Gy; 4 × ABVD + 20Gy; 2 × ABVD + 30Gy; 2 × ABVD + 20Gy. All patients had their initial histology reviewed by a lymphoma expert panel. Documentation was complete in more than 99,1% of cases for this final analysis. Results: Patients were equally balanced for age, gender, stage, histology, performance status and risk factors between arms. There were significant differences in major toxicity (WHO grade III/IV) between 4 × ABVD and 2 × ABVD in the overall number of events (52% vs 33%) including leukopenia (24% vs 15%) and hair loss (28% vs 15%). In terms of radiation dose, there also was a difference in toxicity between 30Gy and 20Gy IFRT (all events: 8.7% vs 2.9%), dysphagia (3% vs 2%), mucositis (3.4% vs 0.7%). Complete remission was achieved in 97% of patients treated with 4 × ABVD, 97% with 2 × ABVD, 99% after 30Gy and 97% after 20Gy. With a median follow-up of 79–91 months, there was no significant difference between 4 × ABVD and 2 × ABVD in terms of overall survival at 5 years (OS: 4 × ABVD 97.1%; 2 × ABVD: 96.6%), freedom from treatment failure (FFTF: 93.0% vs 91.1%) and progression free survival (PFS: 93.5% vs 91.2%). For the radiotherapy question, there were also no significant differences between patients receiving 30Gy IFRT and those with 20Gy IFRT in terms of OS (97.6% vs 97.5%), FFTF (93.4% vs 92.9%) and PFS (93.7% vs 93.2%), respectively. Importantly, there was also no significant difference in terms of OS, FFTF and PFS when all four arms were compared. Conclusion: Two cycles of ABVD followed by 20Gy IFRT is the new GHSG standard of care for Hodgkin patients in early favourable stages. Disclosures: No relevant conflicts of interest to declare.

Intensified Chemotherapy and Dose-Reduced Involved-Field Radiotherapy in Patients With Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD11 Trial

2010 ◽  
Vol 28 (27) ◽  
pp. 4199-4206 ◽  
Author(s):  
Hans Theodor Eich ◽  
Volker Diehl ◽  
Helen Görgen ◽  
Thomas Pabst ◽  
Jana Markova ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Intensive Therapy ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Standard Of Care ◽  
Hodgkin's Lymphoma ◽  
Combined Modality Treatment ◽  
Intensified Chemotherapy ◽  
Involved Field ◽  
Involved Field Radiotherapy

PurposeCombined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkin's lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied.Patients and MethodsPatients age 16 to 75 years with newly diagnosed early unfavorable HL were randomly assigned in a 2 × 2 factorial design to one of the following treatment arms: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy of IFRT; four cycles of ABVD + 20 Gy of IFRT; four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPbaseline) + 30 Gy of IFRT; or four cycles of BEACOPPbaseline+ 20 Gy of IFRT.ResultsWith a total of 1,395 patients included, the freedom from treatment failure (FFTF) at 5 years was 85.0%, overall survival was 94.5%, and progression-free survival was 86.0%. BEACOPPbaselinewas more effective than ABVD when followed by 20 Gy of IFRT (5-year FFTF difference, 5.7%; 95% CI, 0.1% to 11.3%). However, there was no difference between BEACOPPbaselineand ABVD when followed by 30 Gy of IFRT (5-year FFTF difference, 1.6%; 95% CI, −3.6% to 6.9%). Similar results were observed for the radiotherapy question; after four cycles of BEACOPPbaseline, 20 Gy was not inferior to 30 Gy (5-year FFTF difference, −0.8%; 95% CI, −5.8% to 4.2%), whereas inferiority of 20 Gy cannot be excluded after four cycles of ABVD (5-year FFTF difference, −4.7%; 95% CI, −10.3% to 0.8%). Treatment-related toxicity occurred more often in the arms with more intensive therapy.ConclusionModerate dose escalation using BEACOPPbaselinedid not significantly improve outcome in early unfavorable HL. Four cycles of ABVD should be followed by 30 Gy of IFRT.

scholarly journals Predicted Risks of Cardiovascular Disease Following Chemotherapy and Radiotherapy in the UK NCRI RAPID Trial of Positron Emission Tomography–Directed Therapy for Early-Stage Hodgkin Lymphoma

2021 ◽  
pp. JCO.21.00408
Author(s):  
David J. Cutter ◽  
Johanna Ramroth ◽  
Patricia Diez ◽  
Andy Buckle ◽  
Georgios Ntentas ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Positron Emission Tomography ◽  
Cardiovascular Risk ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Emission Tomography ◽  
Positron Emission ◽  
Increased Risk ◽  
Involved Field ◽  
Involved Field Radiotherapy

PURPOSE The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL. METHODS We predicted 30-year absolute cardiovascular risk from chemotherapy and involved field radiotherapy in patients who were positron emission tomography (PET)–negative following three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy within a UK randomized trial of PET-directed therapy for ES-HL. Cardiac and carotid radiation doses and chemotherapy exposure were combined with established dose-response relationships and population-based mortality and incidence rates. RESULTS Average mean heart dose was 4.0 Gy (range 0.1-24.0 Gy) and average bilateral common carotid artery dose was 21.5 Gy (range 0.6-38.1 Gy), based on individualized cardiovascular dosimetry for 144 PET-negative patients receiving involved field radiotherapy. The average predicted 30-year radiation-related absolute excess overall cardiovascular mortality was 0.56% (range 0.01%-6.79%; < 0.5% in 67% of patients and > 1% in 15%), whereas average predicted 30-year excess incidence was 6.24% (range 0.31%-31.09%; < 5% in 58% of patients and > 10% in 24%). For cardiac disease, the average predicted 30-year radiation-related absolute excess mortality was 0.42% (0.79% with mediastinal involvement and 0.05% without) and for stroke, it was 0.14%. CONCLUSION Predicted excess cardiovascular risk is small for most patients, so radiotherapy may provide net benefit. However, for a minority of patients receiving high doses of radiation to cardiovascular structures, it may be preferable to consider advanced radiotherapy techniques to reduce doses or to omit radiotherapy and accept the increased relapse risk. Individual assessment of cardiovascular and other risks before treatment would allow personalized decision making about radiotherapy in ES-HL.

Stanford V chemotherapy and involved field radiotherapy for children and adolescents with unfavorable risk Hodgkin lymphoma: Results of a multi-institutional prospective clinical trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9502-9502 ◽  
Author(s):  
Monika Metzger ◽  
Amy Billett ◽  
Alison M. Friedmann ◽  
Matthew J. Krasin ◽  
Scott C. Howard ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Children And Adolescents ◽  
Hodgkin Lymphoma ◽  
Low Dose ◽  
Massachusetts General Hospital ◽  
Children's Hospital ◽  
Significant Difference ◽  
Children’S Hospital ◽  
Involved Field ◽  
Involved Field Radiotherapy

9502 Background: To evaluate the efficacy of 12 weeks of Stanford V chemotherapy (prednisone, vinblastine, doxorubicine, nitrogen mustard, etoposide, vincristine, and bleomycin) without routine growth factor support plus response-adapted low-dose, involved-field radiotherapy (IFRT) in children and adolescents with unfavorable risk Hodgkin lymphoma (HL). Methods: Multi-institutional (St. Jude Children’s Research Hospital, Stanford University, Children’s Hospital Boston, Massachusetts General Hospital and Maine Children’s Hospital) clinical trial. One hundred forty-one patients with clinical stages IIB (n=43), IIIB (n=19), IVA (n=27), and IVB (n=52) HL were treated with 12 weeks of Stanford V chemotherapy and low dose IFRT between June 2002 and May 2011. Involved nodal sites in complete remission (CR, defined as > 75% shrinkage of the original tumor and PET negative) after 8 weeks of Stanford V received 15 Gy IFRT; those sites that achieved only partial response received 25.5 Gy IFRT after completion of all 12 weeks of chemotherapy. Results: With a median follow-up of 4.6 years, the 3-year overall and event-free survival (EFS) are 97% (SE=2%) and 79% (SE=4%) respectively. There was no significant difference in EFS by stage (IIB vs. IIIB vs. IV; P=0.84). Ten patients developed progessive disease and 18 relapsed, while 5 have died (1 after relapse in an accident and 4 of refractory disease). Most common toxicities were grade 3 hematologic with 234 episodes of neutropenia in 101 patients (72%) and 85 episodes of anemia in 52 patients (37%); Fever and neutropenia occurred 13 times in 12 patients (9%). Conclusions: Risk-adapted, combined-modality therapy using 12 weeks of Stanford V chemotherapy plus IFRT is well tolerated in this population with manageable acute toxicities. Overall survival is comparable to other more intense chemotherapy regimens. Future high-risk front line therapies may consider a Stanford V backbone with targeted intensification and further tailoring of radiation therapy.

scholarly journals Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial

2013 ◽  
Vol 24 (4) ◽  
pp. 1044-1048 ◽  
Author(s):  
R.H. Advani ◽  
R.T. Hoppe ◽  
D. Baer ◽  
J. Mason ◽  
R. Warnke ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Involved Field ◽  
Involved Field Radiotherapy

Biology, Clinical Course and Management of Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Hematology ◽  
2006 ◽  
Vol 2006 (1) ◽  
pp. 266-272 ◽  
Author(s):  
Lucia Nogová ◽  
Thomas Rudiger ◽  
Andreas Engert
Keyword(s):  
Risk Factors ◽  
Adverse Effects ◽  
Hodgkin Lymphoma ◽  
Clinical Presentation ◽  
Early Stage ◽  
Combined Modality Treatment ◽  
Early Stages ◽  
If Technique ◽  
Extended Field ◽  
Involved Field

Abstract Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) differs in histological and clinical presentation from classical Hodgkin lymphoma (cHL). The typical morphologic signs of NLPHL are atypical “lymphocytic and histiocytic” (L&H) cells, which are surrounded by a non-neoplastic nodular background of small lymphocytes of B-cell origin. The NLPHL cells are positive for CD45, CD19, CD20, CD22 and CD79a, but lack expression of CD15 and CD30, the typical markers for cHL. NLPHL patients are predominantly of male gender with a median age of 37 years. Patients often present in early stages (63%) and rarely have B-symptoms (9%). Treatment of NLPHL patients using standard Hodgkin lymphoma (HL) protocols leads to complete remission (CR) in more than 95% of patients. Survival and freedom from treatment failure (FFTF) are worse in advanced-stage patients than in early-stage patients. Thus, patients in advanced and in early stages with unfavorable risk factors are treated similarly to cHL patients. In contrast, patients with early-stage NLPHL without risk factors can be sufficiently treated with reduced intensity programs having less severe adverse effects. As a result, treatment of early NLPHL is less clearly defined, including radiotherapy in extended field (EF) or involved field (IF) technique, combined modality treatment, and, more recently, monoclonal antibody rituximab. Watch and wait strategy plays an important role in pediatric oncology to avoid adverse effects associated with therapy.

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