Dose-Intensification in Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD14 Trial

Purpose In patients with early unfavorable Hodgkin's lymphoma (HL), combined modality treatment with four cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) and 30 Gy involved-field radiotherapy (IFRT) results in long-term tumor control of approximately 80%. We aimed to improve these results using more intensive chemotherapy. Patients and Methods Patients with newly diagnosed early unfavorable HL were randomly assigned to either four cycles of ABVD or an intensified treatment consisting of two cycles of escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by two cycles of ABVD (2 + 2). Chemotherapy was followed by 30 Gy IFRT in both arms. The primary end point was freedom from treatment failure (FFTF); secondary end points included progression-free survival (PFS) and treatment-related toxicity. Results With a total of 1,528 qualified patients included, the 2 + 2 regimen demonstrated superior FFTF compared with four cycles of ABVD (P < .001; hazard ratio, 0.44; 95% CI, 0.30 to 0.66), with a difference of 7.2% at 5 years (95% CI, 3.8 to 10.5). The difference in 5-year PFS was 6.2% (95% CI, 3.0% to 9.5%). There was more acute toxicity associated with 2 + 2 than with ABVD, but there were no overall differences in treatment-related mortality or secondary malignancies. Conclusion Intensified chemotherapy with two cycles of BEACOPP escalated followed by two cycles of ABVD followed by IFRT significantly improves tumor control in patients with early unfavorable HL.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2010.29.8018 ◽

2010 ◽

Vol 28 (27) ◽

pp. 4199-4206 ◽

Cited By ~ 274

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.

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Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma

Annals of Oncology ◽

10.1093/annonc/mds110 ◽

2012 ◽

Vol 23 (11) ◽

pp. 2953-2959 ◽

Cited By ~ 26

Author(s):

S. Sasse ◽

B. Klimm ◽

H. Görgen ◽

M. Fuchs ◽

A. Heyden-Honerkamp ◽

...

Keyword(s):

Hodgkin’S Lymphoma ◽

Early Stage ◽

Hodgkin's Lymphoma ◽

Combined Modality Treatment ◽

Combined Modality ◽

Involved Field ◽

Involved Field Radiotherapy

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Evaluation of Early Stage Hodgkin’s Lymphoma Treatment: Two Decades of Progress.

Blood ◽

10.1182/blood.v104.11.4581.4581 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4581-4581

Author(s):

Eyad F. Alsaeed ◽

Rajiv Samant ◽

Gallant Victor ◽

Lother Huebsch ◽

Wayne Kendal

Keyword(s):

Overall Survival ◽

Treatment Modality ◽

Hodgkin’S Lymphoma ◽

Early Stage ◽

Disease Free Survival ◽

Hodgkin's Lymphoma ◽

Combined Modality Treatment ◽

Combined Modality ◽

Involved Field ◽

Disease Free

Abstract Introduction The treatment of early stage Hodgkin’s lymphoma is controversial. Radiotherapy alone, chemotherapy alone or a combination of radiotherapy and chemotherapy are all considered effective options. Purpose The purpose of this study is to review the treatment approaches and outcomes used for early stage Hodgkin’s lymphoma over the past two decades at ORCC Methods Retrospective chart review of all patients with stage IA /IIA treated from 1984–2002 was performed. Patients were separated into three groups according to initial treatment modality: radiation alone (Rads), chemotherapy alone (Chemo), or combined modality (Combined). Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis. Result Between May 1984 and January 2003, 172 patients with newly diagnosed Hodgkin’s lymphoma (28% stage 1A, 72% stage 2A) were seen at our centre. Treatment was as follows: 49% Rads, 13% Chemo and 38% Combined. The median age was 33.7 years (range: 17 – 82 years) and the median follow-up of 73 months (range: 3 – 204 months). The 5-year disease free and overall survival rates for the entire group were 90% and 96 % respectively. The 5-year disease-free and overall survival by treatment modality was: Rads 87% and 93 %; Chemo 80 % and 100 %; Combined 97 % and 98%. In the Combined group, there was no difference in outcome between patients receiving involved-field radiation and those receiving extended-field radiotherapy. The relapse rate in a patient who received abbreviated chemotherapy and greater than four cycles was 4.3% (1 out of 23) and 2.4% (1 out of 41) respectively. The incidence of acute Grade 3 and 4 toxicities were 9 % and 0.5% respectively. Conclusions Our data confirms the excellent prognosis of early stage Hodgkin’s lymphoma with all the approaches used at our centre. At present, we favour combined modality treatment with involved-field radiotherapy and our results support its continued use.

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Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

Haematologica ◽

10.3324/haematol.2009.015644 ◽

2009 ◽

Vol 95 (3) ◽

pp. 494-500 ◽

Cited By ~ 73

Author(s):

C. Herbst ◽

F. A. Rehan ◽

C. Brillant ◽

J. Bohlius ◽

N. Skoetz ◽

...

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Hodgkin’S Lymphoma ◽

Early Stage ◽

Hodgkin's Lymphoma ◽

Tumor Control ◽

Combined Modality Treatment ◽

Combined Modality

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Escalated-Dose BEACOPP in the Treatment of Patients With Advanced-Stage Hodgkin's Lymphoma: 10 Years of Follow-Up of the GHSG HD9 Study

Journal of Clinical Oncology ◽

10.1200/jco.2008.19.8820 ◽

2009 ◽

Vol 27 (27) ◽

pp. 4548-4554 ◽

Cited By ~ 314

Author(s):

Andreas Engert ◽

Volker Diehl ◽

Jeremy Franklin ◽

Andreas Lohri ◽

Bernd Dörken ◽

...

Keyword(s):

Hodgkin’S Lymphoma ◽

Standard Of Care ◽

Hodgkin's Lymphoma ◽

Secondary Malignancy ◽

Tumor Control ◽

Advanced Stage ◽

Different Doses ◽

Better Than

Purpose The HD9 trial of the German Hodgkin Study Group compared two different doses (baseline and escalated) of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) chemotherapy regimen in 1,196 patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 5 years median follow-up had indicated improved tumor control with BEACOPP escalated. Since the long-term safety and efficacy of this regimen has been debated, we report the 10-year follow-up. Patients and Methods Patients received one of three chemotherapy regimens: eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); eight cycles of BEACOPP baseline; or eight cycles of BEACOPP escalated. Results Median follow-up was 111 months. At 10 years, freedom from treatment failure (FFTF) was 64%, 70%, and 82% with OS rates of 75%, 80%, and 86% for patients treated with COPP/ABVD (arm A), BEACOPP baseline (arm B), and BEACOPP escalated (arm C), respectively (P < .001). BEACOPP escalated was significantly better than BEACOPP baseline in terms of FFTF (P < .0001) and OS (P = .0053). A total of 74 second malignancies (6.2%) were documented, including acute myeloid leukemia (0.4%, 1.5%, and 3.0%), non-Hodgkin's lymphoma (2.7%, 1.7%, and 1.0%), and solid tumors (2.7%, 3.4%, and 1.9%). The corresponding overall secondary malignancy rates were 5.7%, 6.6%, and 6.0%, respectively. Conclusion The 10-year follow-up of the HD9 trial demonstrates a stabilized significant improvement in long-term FFTF and OS for BEACOPP escalated in advanced-stage HL. These results challenge ABVD as standard of care for this patient population.

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Combined Modality Treatment of Two or Four Cycles of ABVD Followed by Involved Field Radiotherapy in the Treatment of Patients with Early Stage Hodgkin’s Lymphoma: Update Interim Analysis of the Randomised HD10 Study of the German Hodgkin Study Group (GHSG).

Blood ◽

10.1182/blood.v106.11.2673.2673 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2673-2673 ◽

Cited By ~ 17

Author(s):

Andreas Engert ◽

Annette Pluetschow ◽

Hans T. Eich ◽

Richard Herrmann ◽

Bernd Doerken ◽

...

Keyword(s):

Overall Survival ◽

Interim Analysis ◽

Hodgkin’S Lymphoma ◽

Early Stage ◽

Hodgkin's Lymphoma ◽

Combined Modality Treatment ◽

Involved Field ◽

Radiotherapy Dose ◽

Involved Field Radiotherapy

Abstract Combined modality treatment is regarded as standard by most study groups for patients with early-stage Hodgkin’s lymphoma (HL). However, the optimal chemotherapy, the number of cycles needed and the optimal radiotherapy dose is still unclear. The GHSG thus conducted a randomised study for patients with early stage favourable Hodgkin’s lymphoma (HD10) in which these questions were addressed. A total of 1370 patients were randomised from 5/1998 to 1/2003 between two or four cycles of ABVD and independently to 20Gy or 30Gy involved field (IF) radiotherapy. For the second interim analysis at a median follow up of 28 months, 847 patients were available. Patients were equally balanced for age, gender, stage, histology, performance status and risk factors. Compared with two cycles, there was more toxicity in patients receiving four cycles of ABVD for leucopenia, hair loss and infection. Concerning radiotherapy dose, there was more toxicity associated with 30Gy for dysphagia, mucositis and leucopenia. The rate of complete remissions ranged between 98% and 99% with no significant differences among treatment arms. Freedom from treatment failure (FFTF) and overall survival showed no differences between the four treatment arms. The curves for overall survival and FFTF were nearly superimposable for all four arms. This analysis suggests that 2 chemotherapy cycles with involved field radiotherapy may be sufficient for patients with early favourable HL, but a reliable assessment must await the final analysis including all randomised patients and with adequate follow-up. The results of the third interim analysis (10/2005) including 1110 patients with a median follow up of more than 3 years will be presented.

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Two Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine Plus Extended-Field Radiotherapy Is Superior to Radiotherapy Alone in Early Favorable Hodgkin's Lymphoma: Final Results of the GHSG HD7 Trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.07.0482 ◽

2007 ◽

Vol 25 (23) ◽

pp. 3495-3502 ◽

Cited By ~ 196

Author(s):

Andreas Engert ◽

Jeremy Franklin ◽

Hans Theodor Eich ◽

Corinne Brillant ◽

Susanne Sehlen ◽

...

Keyword(s):

Hodgkin’S Lymphoma ◽

Complete Response Rate ◽

Complete Response ◽

Observation Time ◽

Hodgkin's Lymphoma ◽

Combined Modality Treatment ◽

Radiotherapy Alone ◽

Extended Field ◽

Involved Field ◽

To Receive

PurposeTo investigate whether combined-modality treatment (CMT) with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by extended-field radiotherapy (EF-RT) is superior to EF-RT alone in patients with early favorable Hodgkin's lymphoma (HL).Patients and MethodsBetween 1993 and 1998, 650 patients with newly diagnosed, histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and randomly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field (arm A) or two cycles of ABVD followed by the same radiotherapy (arm B).ResultsAt a median observation time of 87 months, there was no difference between treatment arms in terms of complete response rate (arm A, 95%; arm B, 94%) and overall survival (at 7 years: arm A, 92%; arm B, 94%; P = .43). However, freedom from treatment failure was significantly different, with 7-year rates of 67% in arm A (95% CI, 61% to 73%) and 88% in arm B (95% CI, 84% to 92%; P ≤ .0001). This was due mainly to significantly more relapses after EF-RT only (arm A, 22%; arm B, 3%). No patient treated with CMT experienced relapse before year 3. Relapses were treated mainly with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, or with the combination cyclophosphamide, vincristine, procarbazine, and prednisone/ABVD; treatment of relapse was significantly more successful in arm A than in arm B (P = .017). In total, there were 39 second malignancies, with 21 in arm A and 18 in arm B, respectively. The incidence was approximately 0.8% per year during years 2 to 9 and was highest in older patients (P < .0001) and those with “B” symptoms (P = .012).ConclusionCMT consisting of two cycles of ABVD plus EF-RT is more effective than EF-RT alone.

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