Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma

P. Johnson, M. Federico, P. A. Kirkwood, A. Fosså, Leanne Berkahn, A. Carella, F. D'Amore, Gunilla Enblad, A. Franceschetto, Michael J. Fulham, S. Luminari, MarkG O'Doherty, Pip Patrick, J. T. Roberts, Gamal Sidra, R. L. Stevens, P. Smith, Judith Trotman, Zaid Viney, J. Radford & 1 others Sally F. Barrington

Research output: Contribution to journalArticle

Abstract

BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PETCT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. © Copyright 2016 Massachusetts Medical Society. All rights reserved.
Original languageEnglish
Pages (from-to)2419-2429
Number of pages11
JournalNew England Journal of Medicine
Volume374
Issue number25
DOIs
Publication statusPublished - 2016

Fingerprint

Hodgkin Disease
Survival Rate
Disease-Free Survival
Bleomycin
Confidence Intervals
Therapeutics
Doxorubicin
Procarbazine
Drug Therapy
Dacarbazine
Vinblastine
Positron Emission Tomography Computed Tomography
Poisons
Medical Societies
Vincristine
Etoposide
Prednisone
Cyclophosphamide
Radiotherapy
Lung

Keywords

  • bleomycin
  • brentuximab vedotin
  • cyclophosphamide
  • dacarbazine
  • doxorubicin
  • etoposide
  • fluorodeoxyglucose f 18
  • prednisone
  • procarbazine
  • vinblastine
  • vincristine
  • antineoplastic agent
  • adult
  • advanced cancer
  • age distribution
  • Article
  • cancer combination chemotherapy
  • cancer mortality
  • cancer prognosis
  • cancer radiotherapy
  • cancer staging
  • cancer survival
  • cardiovascular disease
  • computer assisted emission tomography
  • controlled study
  • drug efficacy
  • dyspnea
  • fatigue
  • febrile neutropenia
  • female
  • fever
  • follow up
  • Hodgkin disease
  • human
  • image analysis
  • interim positron emission tomography computed tomography
  • lung disease
  • major clinical study
  • male
  • middle aged
  • multicenter study
  • multiple cycle treatment
  • neurologic disease
  • neutropenia
  • outcome assessment
  • overall survival
  • pneumonia
  • priority journal
  • progression free survival
  • randomized controlled trial
  • survival rate
  • survival time
  • thrombocytopenia
  • thromboembolism
  • treatment planning
  • treatment response
  • young adult
  • adolescent
  • clinical trial
  • computer assisted tomography
  • disease free survival
  • mortality
  • positron emission tomography
  • prospective study
  • radiography
  • scintiscanning
  • treatment outcome
  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols
  • Bleomycin
  • Dacarbazine
  • Disease-Free Survival
  • Doxorubicin
  • Female
  • Hodgkin Disease
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Prospective Studies
  • Survival Rate
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vinblastine
  • Young Adult

Cite this

Johnson, P., Federico, M., Kirkwood, P. A., Fosså, A., Berkahn, L., Carella, A., ... Barrington, S. F. (2016). Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. New England Journal of Medicine, 374(25), 2419-2429. https://doi.org/10.1056/NEJMoa1510093

Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. / Johnson, P.; Federico, M.; Kirkwood, P. A.; Fosså, A.; Berkahn, Leanne; Carella, A.; D'Amore, F.; Enblad, Gunilla; Franceschetto, A.; Fulham, Michael J.; Luminari, S.; O'Doherty, MarkG; Patrick, Pip; Roberts, J. T.; Sidra, Gamal; Stevens, R. L.; Smith, P.; Trotman, Judith; Viney, Zaid; Radford, J.; Barrington, Sally F.

In: New England Journal of Medicine, Vol. 374, No. 25, 2016, p. 2419-2429.

Research output: Contribution to journalArticle

Johnson, P, Federico, M, Kirkwood, PA, Fosså, A, Berkahn, L, Carella, A, D'Amore, F, Enblad, G, Franceschetto, A, Fulham, MJ, Luminari, S, O'Doherty, M, Patrick, P, Roberts, JT, Sidra, G, Stevens, RL, Smith, P, Trotman, J, Viney, Z, Radford, J & Barrington, SF 2016, 'Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma', New England Journal of Medicine, vol. 374, no. 25, pp. 2419-2429. https://doi.org/10.1056/NEJMoa1510093
Johnson, P. ; Federico, M. ; Kirkwood, P. A. ; Fosså, A. ; Berkahn, Leanne ; Carella, A. ; D'Amore, F. ; Enblad, Gunilla ; Franceschetto, A. ; Fulham, Michael J. ; Luminari, S. ; O'Doherty, MarkG ; Patrick, Pip ; Roberts, J. T. ; Sidra, Gamal ; Stevens, R. L. ; Smith, P. ; Trotman, Judith ; Viney, Zaid ; Radford, J. ; Barrington, Sally F. / Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 25. pp. 2419-2429.
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abstract = "BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PETCT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7{\%}) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7{\%} (95{\%} confidence interval [CI], 82.1 to 88.6) and 97.2{\%} (95{\%} CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4{\%} (95{\%} CI, 80.7 to 87.5) and 97.6{\%} (95{\%} CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95{\%} CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4{\%} had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5{\%} and the overall survival rate 87.8{\%}. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6{\%} and an overall survival rate of 95.8{\%}. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. {\circledC} Copyright 2016 Massachusetts Medical Society. All rights reserved.",
keywords = "bleomycin, brentuximab vedotin, cyclophosphamide, dacarbazine, doxorubicin, etoposide, fluorodeoxyglucose f 18, prednisone, procarbazine, vinblastine, vincristine, antineoplastic agent, adult, advanced cancer, age distribution, Article, cancer combination chemotherapy, cancer mortality, cancer prognosis, cancer radiotherapy, cancer staging, cancer survival, cardiovascular disease, computer assisted emission tomography, controlled study, drug efficacy, dyspnea, fatigue, febrile neutropenia, female, fever, follow up, Hodgkin disease, human, image analysis, interim positron emission tomography computed tomography, lung disease, major clinical study, male, middle aged, multicenter study, multiple cycle treatment, neurologic disease, neutropenia, outcome assessment, overall survival, pneumonia, priority journal, progression free survival, randomized controlled trial, survival rate, survival time, thrombocytopenia, thromboembolism, treatment planning, treatment response, young adult, adolescent, clinical trial, computer assisted tomography, disease free survival, mortality, positron emission tomography, prospective study, radiography, scintiscanning, treatment outcome, Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols, Bleomycin, Dacarbazine, Disease-Free Survival, Doxorubicin, Female, Hodgkin Disease, Humans, Male, Middle Aged, Positron-Emission Tomography, Prospective Studies, Survival Rate, Tomography, X-Ray Computed, Treatment Outcome, Vinblastine, Young Adult",
author = "P. Johnson and M. Federico and Kirkwood, {P. A.} and A. Foss{\aa} and Leanne Berkahn and A. Carella and F. D'Amore and Gunilla Enblad and A. Franceschetto and Fulham, {Michael J.} and S. Luminari and MarkG O'Doherty and Pip Patrick and Roberts, {J. T.} and Gamal Sidra and Stevens, {R. L.} and P. Smith and Judith Trotman and Zaid Viney and J. Radford and Barrington, {Sally F.}",
note = "Cited By :20 Export Date: 16 March 2017 CODEN: NEJMA Correspondence Address: Johnson, P.; Cancer Research UK Centre, University of Southampton, Southampton General Hospital, Somers Cancer Research Bldg., United Kingdom; email: johnsonp@soton.ac.uk Chemicals/CAS: bleomycin, 11056-06-7, 9041-93-4; brentuximab vedotin, 914088-09-8; cyclophosphamide, 50-18-0; dacarbazine, 4342-03-4; doxorubicin, 23214-92-8, 25316-40-9; etoposide, 33419-42-0; fluorodeoxyglucose f 18, 63503-12-8; prednisone, 53-03-2; procarbazine, 366-70-1, 671-16-9; vinblastine, 865-21-4; vincristine, 57-22-7; Bleomycin; Dacarbazine; Doxorubicin; Vinblastine Funding details: CRUK/07/033, Cancer Research UK Funding text: Supported by Cancer Research UK (reference CRUK/07/033), Leukaemia and Blood Cancer New Zealand, and Cancer Australia. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. References: Bonadonna, G., Zucali, R., Monfardini, S., De Lena, M., Uslenghi, C., Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP (1975) Cancer, 36, pp. 252-259; Canellos, G.P., Anderson, J.R., Propert, K.J., Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD (1992) N Engl J Med, 327, pp. 1478-1484; Viviani, S., Bonadonna, G., Santoro, A., Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: Ten-year results (1996) J Clin Oncol, 14, pp. 1421-1430; Duggan, D.B., Petroni, G.R., Johnson, J.L., Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: Report of an intergroup trial (2003) J Clin Oncol, 21, pp. 607-614; Johnson, P.W.M., Radford, J.A., Cullen, M.H., Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: Results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519) (2005) J Clin Oncol, 23, pp. 9208-9218; Hoskin, P.J., Lowry, L., Horwich, A., Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin's lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244 (2009) J Clin Oncol, 27, pp. 5390-5396; Gordon, L.I., Hong, F., Fisher, R.I., Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advancedstage Hodgkin lymphoma: An intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496) (2013) J Clin Oncol, 31, pp. 684-691; Engert, A., Diehl, V., Franklin, J., Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study (2009) J Clin Oncol, 27, pp. 4548-4554; Mounier, N., Brice, P., Bologna, S., ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): Final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial (2014) Ann Oncol, 25, pp. 1622-1628; Viviani, S., Zinzani, P.L., Rambaldi, A., ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned (2011) N Engl J Med, 365, pp. 203-212; Skoetz, N., Trelle, S., Rancea, M., Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: A systematic review and network meta-analysis (2013) Lancet Oncol, 14, pp. 943-952; Behringer, K., Mueller, H., Goergen, H., Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials (2013) J Clin Oncol, 31, pp. 231-239; Eichenauer, D.A., Thielen, I., Haverkamp, H., Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: A report from the German Hodgkin Study Group (2014) Blood, 123, pp. 1658-1664; Martin, W.G., Ristow, K.M., Habermann, T.M., Colgan, J.P., Witzig, T.E., Ansell, S.M., Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin's lymphoma (2005) J Clin Oncol, 23, pp. 7614-7620; Gallamini, A., Hutchings, M., Rigacci, L., Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: A report from a joint Italian-Danish study (2007) J Clin Oncol, 25, pp. 3746-3752; Barrington, S.F., Mackewn, J.E., Schleyer, P., Establishment of a UK-wide network to facilitate the acquisition of quality assured FDG-PET data for clinical trials in lymphoma (2011) Ann Oncol, 22, pp. 739-745; Barrington, S.F., Qian, W., Somer, E.J., Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma (2010) Eur J Nucl Med Mol Imaging, 37, pp. 1824-1833; Barrington, S.F., Mikhaeel, N.G., Kostakoglu, L., Role of imaging in the staging and response assessment of lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group (2014) J Clin Oncol, 32, pp. 3048-3058; Boleti, E., Mead, G.M., ABVD for Hodgkin's lymphoma: Full-dose chemotherapy without dose reductions or growth factors (2007) Ann Oncol, 18, pp. 376-380; Evens, A.M., Cilley, J., Ortiz, T., G-CSF is not necessary to maintain over 99{\%} dose-intensity with ABVD in the treatment of Hodgkin lymphoma: Low toxicity and excellent outcomes in a 10-year analysis (2007) Br J Haematol, 137, pp. 545-552; Behringer, K., Goergen, H., Hitz, F., Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): An open-label, randomised, non-inferiority trial (2015) Lancet, 385, pp. 1418-1427; Press, O.W., Li, H., Schoder, H., US intergroup trial of response-adapted therapy for stage III to IV Hodgkin lymphoma using early interim fluorodeoxyglucose-positron emission tomography imaging: Southwest Oncology Group S0816 (2016) J Clin Oncol, , April 11 Epub ahead of print; Gallamini, A., Rossi, A., Patti, C., Interim PET-adapted chemotherapy in advanced Hodgkin lymphoma (HL): Results of the second interim analysis of the Italian GITIL/FIL HD0607 Trial (2015) Hematol Oncol, 33 S, p. 163. , abstract; Hutchings, M., Kostakoglu, L., Zaucha, J.M., In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma (2014) J Clin Oncol, 32, pp. 2705-2711; Scott, D.W., Chan, F.C., Hong, F., Gene expression-based model using formalinfixed paraffin-embedded biopsies predicts overall survival in advancedstage classical Hodgkin lymphoma (2013) J Clin Oncol, 31, pp. 692-700; Steidl, C., Lee, T., Shah, S.P., Tumorassociated macrophages and survival in classic Hodgkin's lymphoma (2010) N Engl J Med, 362, pp. 875-885; Engert, A., Haverkamp, H., Kobe, C., Reduced-intensity chemotherapy and PETguided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): A randomised, open-label, phase 3 non-inferiority trial (2012) Lancet, 379, pp. 1791-1799",
year = "2016",
doi = "10.1056/NEJMoa1510093",
language = "English",
volume = "374",
pages = "2419--2429",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "25",

}

TY - JOUR

T1 - Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma

AU - Johnson, P.

AU - Federico, M.

AU - Kirkwood, P. A.

AU - Fosså, A.

AU - Berkahn, Leanne

AU - Carella, A.

AU - D'Amore, F.

AU - Enblad, Gunilla

AU - Franceschetto, A.

AU - Fulham, Michael J.

AU - Luminari, S.

AU - O'Doherty, MarkG

AU - Patrick, Pip

AU - Roberts, J. T.

AU - Sidra, Gamal

AU - Stevens, R. L.

AU - Smith, P.

AU - Trotman, Judith

AU - Viney, Zaid

AU - Radford, J.

AU - Barrington, Sally F.

N1 - Cited By :20 Export Date: 16 March 2017 CODEN: NEJMA Correspondence Address: Johnson, P.; Cancer Research UK Centre, University of Southampton, Southampton General Hospital, Somers Cancer Research Bldg., United Kingdom; email: johnsonp@soton.ac.uk Chemicals/CAS: bleomycin, 11056-06-7, 9041-93-4; brentuximab vedotin, 914088-09-8; cyclophosphamide, 50-18-0; dacarbazine, 4342-03-4; doxorubicin, 23214-92-8, 25316-40-9; etoposide, 33419-42-0; fluorodeoxyglucose f 18, 63503-12-8; prednisone, 53-03-2; procarbazine, 366-70-1, 671-16-9; vinblastine, 865-21-4; vincristine, 57-22-7; Bleomycin; Dacarbazine; Doxorubicin; Vinblastine Funding details: CRUK/07/033, Cancer Research UK Funding text: Supported by Cancer Research UK (reference CRUK/07/033), Leukaemia and Blood Cancer New Zealand, and Cancer Australia. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. References: Bonadonna, G., Zucali, R., Monfardini, S., De Lena, M., Uslenghi, C., Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP (1975) Cancer, 36, pp. 252-259; Canellos, G.P., Anderson, J.R., Propert, K.J., Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD (1992) N Engl J Med, 327, pp. 1478-1484; Viviani, S., Bonadonna, G., Santoro, A., Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: Ten-year results (1996) J Clin Oncol, 14, pp. 1421-1430; Duggan, D.B., Petroni, G.R., Johnson, J.L., Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: Report of an intergroup trial (2003) J Clin Oncol, 21, pp. 607-614; Johnson, P.W.M., Radford, J.A., Cullen, M.H., Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: Results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519) (2005) J Clin Oncol, 23, pp. 9208-9218; Hoskin, P.J., Lowry, L., Horwich, A., Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin's lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244 (2009) J Clin Oncol, 27, pp. 5390-5396; Gordon, L.I., Hong, F., Fisher, R.I., Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advancedstage Hodgkin lymphoma: An intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496) (2013) J Clin Oncol, 31, pp. 684-691; Engert, A., Diehl, V., Franklin, J., Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study (2009) J Clin Oncol, 27, pp. 4548-4554; Mounier, N., Brice, P., Bologna, S., ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): Final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial (2014) Ann Oncol, 25, pp. 1622-1628; Viviani, S., Zinzani, P.L., Rambaldi, A., ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned (2011) N Engl J Med, 365, pp. 203-212; Skoetz, N., Trelle, S., Rancea, M., Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: A systematic review and network meta-analysis (2013) Lancet Oncol, 14, pp. 943-952; Behringer, K., Mueller, H., Goergen, H., Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials (2013) J Clin Oncol, 31, pp. 231-239; Eichenauer, D.A., Thielen, I., Haverkamp, H., Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: A report from the German Hodgkin Study Group (2014) Blood, 123, pp. 1658-1664; Martin, W.G., Ristow, K.M., Habermann, T.M., Colgan, J.P., Witzig, T.E., Ansell, S.M., Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin's lymphoma (2005) J Clin Oncol, 23, pp. 7614-7620; Gallamini, A., Hutchings, M., Rigacci, L., Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: A report from a joint Italian-Danish study (2007) J Clin Oncol, 25, pp. 3746-3752; Barrington, S.F., Mackewn, J.E., Schleyer, P., Establishment of a UK-wide network to facilitate the acquisition of quality assured FDG-PET data for clinical trials in lymphoma (2011) Ann Oncol, 22, pp. 739-745; Barrington, S.F., Qian, W., Somer, E.J., Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma (2010) Eur J Nucl Med Mol Imaging, 37, pp. 1824-1833; Barrington, S.F., Mikhaeel, N.G., Kostakoglu, L., Role of imaging in the staging and response assessment of lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group (2014) J Clin Oncol, 32, pp. 3048-3058; Boleti, E., Mead, G.M., ABVD for Hodgkin's lymphoma: Full-dose chemotherapy without dose reductions or growth factors (2007) Ann Oncol, 18, pp. 376-380; Evens, A.M., Cilley, J., Ortiz, T., G-CSF is not necessary to maintain over 99% dose-intensity with ABVD in the treatment of Hodgkin lymphoma: Low toxicity and excellent outcomes in a 10-year analysis (2007) Br J Haematol, 137, pp. 545-552; Behringer, K., Goergen, H., Hitz, F., Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): An open-label, randomised, non-inferiority trial (2015) Lancet, 385, pp. 1418-1427; Press, O.W., Li, H., Schoder, H., US intergroup trial of response-adapted therapy for stage III to IV Hodgkin lymphoma using early interim fluorodeoxyglucose-positron emission tomography imaging: Southwest Oncology Group S0816 (2016) J Clin Oncol, , April 11 Epub ahead of print; Gallamini, A., Rossi, A., Patti, C., Interim PET-adapted chemotherapy in advanced Hodgkin lymphoma (HL): Results of the second interim analysis of the Italian GITIL/FIL HD0607 Trial (2015) Hematol Oncol, 33 S, p. 163. , abstract; Hutchings, M., Kostakoglu, L., Zaucha, J.M., In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma (2014) J Clin Oncol, 32, pp. 2705-2711; Scott, D.W., Chan, F.C., Hong, F., Gene expression-based model using formalinfixed paraffin-embedded biopsies predicts overall survival in advancedstage classical Hodgkin lymphoma (2013) J Clin Oncol, 31, pp. 692-700; Steidl, C., Lee, T., Shah, S.P., Tumorassociated macrophages and survival in classic Hodgkin's lymphoma (2010) N Engl J Med, 362, pp. 875-885; Engert, A., Haverkamp, H., Kobe, C., Reduced-intensity chemotherapy and PETguided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): A randomised, open-label, phase 3 non-inferiority trial (2012) Lancet, 379, pp. 1791-1799

PY - 2016

Y1 - 2016

N2 - BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PETCT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. © Copyright 2016 Massachusetts Medical Society. All rights reserved.

AB - BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PETCT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. © Copyright 2016 Massachusetts Medical Society. All rights reserved.

KW - bleomycin

KW - brentuximab vedotin

KW - cyclophosphamide

KW - dacarbazine

KW - doxorubicin

KW - etoposide

KW - fluorodeoxyglucose f 18

KW - prednisone

KW - procarbazine

KW - vinblastine

KW - vincristine

KW - antineoplastic agent

KW - adult

KW - advanced cancer

KW - age distribution

KW - Article

KW - cancer combination chemotherapy

KW - cancer mortality

KW - cancer prognosis

KW - cancer radiotherapy

KW - cancer staging

KW - cancer survival

KW - cardiovascular disease

KW - computer assisted emission tomography

KW - controlled study

KW - drug efficacy

KW - dyspnea

KW - fatigue

KW - febrile neutropenia

KW - female

KW - fever

KW - follow up

KW - Hodgkin disease

KW - human

KW - image analysis

KW - interim positron emission tomography computed tomography

KW - lung disease

KW - major clinical study

KW - male

KW - middle aged

KW - multicenter study

KW - multiple cycle treatment

KW - neurologic disease

KW - neutropenia

KW - outcome assessment

KW - overall survival

KW - pneumonia

KW - priority journal

KW - progression free survival

KW - randomized controlled trial

KW - survival rate

KW - survival time

KW - thrombocytopenia

KW - thromboembolism

KW - treatment planning

KW - treatment response

KW - young adult

KW - adolescent

KW - clinical trial

KW - computer assisted tomography

KW - disease free survival

KW - mortality

KW - positron emission tomography

KW - prospective study

KW - radiography

KW - scintiscanning

KW - treatment outcome

KW - Adolescent

KW - Adult

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Bleomycin

KW - Dacarbazine

KW - Disease-Free Survival

KW - Doxorubicin

KW - Female

KW - Hodgkin Disease

KW - Humans

KW - Male

KW - Middle Aged

KW - Positron-Emission Tomography

KW - Prospective Studies

KW - Survival Rate

KW - Tomography, X-Ray Computed

KW - Treatment Outcome

KW - Vinblastine

KW - Young Adult

U2 - 10.1056/NEJMoa1510093

DO - 10.1056/NEJMoa1510093

M3 - Article

VL - 374

SP - 2419

EP - 2429

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 25

ER -