Response-adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children’s Oncology Group
Corresponding Author
Kara M. Kelly
Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA
Correspondence: Kara M. Kelly, Roswell Park Comprehensive Cancer Center, Department of Pediatrics, Elm & Carlton Streets, Buffalo, NY 14263, USA.
E-mail: [email protected]
Search for more papers by this authorPeter D. Cole
Division of Pediatric Hematology/Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
Search for more papers by this authorQinglin Pei
Department of Biostatistics, University of Florida, Children’s Oncology Group, Statistics and Data Center, Gainesville, FL, USA
Search for more papers by this authorRizvan Bush
Children’s Oncology Group, Statistics and Data Center, Monrovia, CA, USA
Search for more papers by this authorKenneth B. Roberts
Department of Therapeutic Radiology, Yale University School of Medicine, Yale-New Haven Hospital, New Haven, CT, USA
Search for more papers by this authorDavid C. Hodgson
Department of Radiation Oncology, University of Toronto, Princess Margaret Hospital, Toronto, Ontario, Canada
Search for more papers by this authorKathleen M. McCarten
Department of Diagnostic Imaging, Warren Alpert Medical School, Brown University, Providence, RI, USA
Search for more papers by this authorSteve Y. Cho
Department of Radiology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
Search for more papers by this authorCindy Schwartz
Division of Pediatric Hematology, Oncology and BMT, Medical College of Wisconsin, Milwaukee, WI, USA
Search for more papers by this authorCorresponding Author
Kara M. Kelly
Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA
Correspondence: Kara M. Kelly, Roswell Park Comprehensive Cancer Center, Department of Pediatrics, Elm & Carlton Streets, Buffalo, NY 14263, USA.
E-mail: [email protected]
Search for more papers by this authorPeter D. Cole
Division of Pediatric Hematology/Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
Search for more papers by this authorQinglin Pei
Department of Biostatistics, University of Florida, Children’s Oncology Group, Statistics and Data Center, Gainesville, FL, USA
Search for more papers by this authorRizvan Bush
Children’s Oncology Group, Statistics and Data Center, Monrovia, CA, USA
Search for more papers by this authorKenneth B. Roberts
Department of Therapeutic Radiology, Yale University School of Medicine, Yale-New Haven Hospital, New Haven, CT, USA
Search for more papers by this authorDavid C. Hodgson
Department of Radiation Oncology, University of Toronto, Princess Margaret Hospital, Toronto, Ontario, Canada
Search for more papers by this authorKathleen M. McCarten
Department of Diagnostic Imaging, Warren Alpert Medical School, Brown University, Providence, RI, USA
Search for more papers by this authorSteve Y. Cho
Department of Radiology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
Search for more papers by this authorCindy Schwartz
Division of Pediatric Hematology, Oncology and BMT, Medical College of Wisconsin, Milwaukee, WI, USA
Search for more papers by this authorSummary
The AHOD0831 study for paediatric patients with high risk Hodgkin lymphoma tested a response-based approach designed to limit cumulative alkylator exposure and reduce radiation volumes. Patients (Stage IIIB/IVB) received two cycles of ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide). Rapid early responders [RER, no positron emission tomography (PET) activity above mediastinal blood pool] were consolidated with 2 cycles of ABVE-PC. Slow early responders (SER) received 2 cycles of ifosfamide/vinorelbine and 2 cycles of ABVE-PC. Radiotherapy was administered to sites of initial bulk and/or SER. By intent-to-treat analysis, 4-year second event-free survival (EFS; freedom from second relapse or malignancy) was 91·9% [95% confidence interval (CI): 86·1–95·3%], below the projected baseline of 95% (P = 0·038). Five-year first EFS and overall survival (OS) rates are 79·1% (95% CI: 71·5–84·8%) and 95% (95% CI: 88·8–97·8%). Eight of 11 SER patients with persistent PET positive lesions at the end of chemotherapy had clinical evidence of active disease (3 biopsy-proven, 5 with progressive disease or later relapses). Although this response-directed approach did not reach the ambitiously high pre-specified target for second EFS, EFS and OS rates are comparable with results of recent trials despite the reduction in radiotherapy volumes from historical involved fields. Persistent PET at end of chemotherapy identifies a cohort at an especially high risk for relapse/early progression.
Conflicts of Interest
The authors declare no competing financial interests.
Supporting Information
Filename | Description |
---|---|
bjh16014-sup-0001-TableS1.docxapplication/docx, 13.1 KB | Table SI. Distribution of Deauville scores of FDG-PET scans at initial staging (PET0), post cycle 1 (PET1) and post cycle 2 (PET2) obtained from post hoc analyses. Deauville scores were only available for cases with adequate DICOM PET/CT images which could be retrospectively reviewed visually and quantitated by PET. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- Borchmann, P., Haverkamp, H., Diehl, V., Cerny, T., Markova, J., Ho, A.D., Eich, H.T., Mueller-Hermelink, H.K., Kanz, L., Greil, R., Rank, A., Paulus, U., Smardova, L., Huber, C., Dorken, B., Nerl, C., Krause, S.W., Mueller, R.P., Fuchs, M. & Engert, A. (2011) Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. Journal of Clinical Oncology, 29, 4234–4242.
- Borchmann, P., Goergen, H., Kobe, C., Lohri, A., Greil, R., Eichenauer, D.A., Zijlstra, J.M., Markova, J., Meissner, J., Feuring-Buske, M., Huttmann, A., Dierlamm, J., Soekler, M., Beck, H.J., Willenbacher, W., Ludwig, W.D., Pabst, T., Topp, M.S., Hitz, F., Bentz, M., Keller, U.B., Kuhnhardt, D., Ostermann, H., Schmitz, N., Hertenstein, B., Aulitzky, W., Maschmeyer, G., Vieler, T., Eich, H., Baues, C., Stein, H., Fuchs, M., Kuhnert, G., Diehl, V., Dietlein, M. & Engert, A. (2018) PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet, 390, 2790–2802.
- Casasnovas, R.-O., Bouabdallah, R., Brice, P., Lazarovici, J., Ghesquieres, H., Stamatoullas, A., Dupuis, J., Gac, A.-C., Gastinne, T., Joly, B., Bouabdallah, K., Nicolas-Virelizier, E., Feugier, P., Morschhauser, F., Delarue, R., Farhat, H., Quittet, P., Berriolo-Riedinger, A., Tempescul, A., Edeline, V., Maisonneuve, H., Fornecker, L.-M., Lamy, T., Delmer, A., Dartigues, P., Martin, L., André, M., Mounier, N., Traverse-Glehen, A. & Meignan, M. (2019) PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study. The Lancet Oncology, 20, 202–215.
- Cheson, B.D., Pfistner, B., Juweid, M.E., Gascoyne, R.D., Specht, L., Horning, S.J., Coiffier, B., Fisher, R.I., Hagenbeek, A., Zucca, E., Rosen, S.T., Stroobants, S., Lister, T.A., Hoppe, R.T., Dreyling, M., Tobinai, K., Vose, J.M., Connors, J.M., Federico, M. & Diehl, V. (2007) Revised response criteria for malignant lymphoma. Journal of Clinical Oncology, 25, 579–586.
- Friedman, D.L., Chen, L., Wolden, S., Buxton, A., McCarten, K., FitzGerald, T.J., Kessel, S., De Alarcon, P.A., Chen, A.R., Kobrinsky, N., Ehrlich, P., Hutchison, R.E., Constine, L.S. & Schwartz, C.L. (2014) Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. Journal of Clinical Oncology, 32, 3651–3658.
- Gordon, L.I., Hong, F., Fisher, R.I., Bartlett, N.L., Connors, J.M., Gascoyne, R.D., Wagner, H., Stiff, P.J., Cheson, B.D., Gospodarowicz, M., Advani, R., Kahl, B.S., Friedberg, J.W., Blum, K.A., Habermann, T.M., Tuscano, J.M., Hoppe, R.T. & Horning, S.J. (2013) Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). Journal of Clinical Oncology, 31, 684–691.
- Harker-Murray, P.D., Drachtman, R.A., Hodgson, D.C., Chauvenet, A.R., Kelly, K.M. & Cole, P.D. (2014) Stratification of treatment intensity in relapsed pediatric Hodgkin lymphoma. Pediatric Blood & Cancer, 61, 579–586.
- Hasenclever, D., Kurch, L., Mauz-Korholz, C., Elsner, A., Georgi, T., Wallace, H., Landman-Parker, J., Moryl-Bujakowska, A., Cepelova, M., Karlen, J., Alvarez Fernandez-Teijeiro, A., Attarbaschi, A., Fossa, A., Pears, J., Hraskova, A., Bergstrasser, E., Beishuizen, A., Uyttebroeck, A., Schomerus, E., Sabri, O., Korholz, D. & Kluge, R. (2014) qPET - a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma. European Journal of Nuclear Medicine and Molecular Imaging, 41, 1301–1308.
- Hodgson, D.C., Hudson, M.M. & Constine, L.S. (2007) Pediatric hodgkin lymphoma: maximizing efficacy and minimizing toxicity. Seminars in Radiation Oncology, 17, 230–242.
- Johnson, P.W., Sydes, M.R., Hancock, B.W., Cullen, M., Radford, J.A. & Stenning, S.P. (2010) Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519). Journal of Clinical Oncology, 28, 3352–3359.
- Johnson, P., Federico, M., Kirkwood, A., Fosså, A., Berkahn, L., Carella, A., d’Amore, F., Enblad, G., Franceschetto, A. & Fulham, M. (2016) Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. New England Journal of Medicine, 374, 2419–2429.
- Josting, A., Rudolph, C., Mapara, M., Glossmann, J.P., Sieniawski, M., Sieber, M., Kirchner, H.H., Dorken, B., Hossfeld, D.K., Kisro, J., Metzner, B., Berdel, W.E., Diehl, V. & Engert, A. (2005) Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG). Annals of Oncology, 16, 116–123.
- Juweid, M.E., Stroobants, S., Hoekstra, O.S., Mottaghy, F.M., Dietlein, M., Guermazi, A., Wiseman, G.A., Kostakoglu, L., Scheidhauer, K., Buck, A., Naumann, R., Spaepen, K., Hicks, R.J., Weber, W.A., Reske, S.N., Schwaiger, M., Schwartz, L.H., Zijlstra, J.M., Siegel, B.A. & Cheson, B.D. & Imaging Subcommittee of International Harmonization Project in Lymphoma. (2007) Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. Journal of Clinical Oncology, 25, 571–578.
- Kelly, K.M. (2015) Hodgkin lymphoma in children and adolescents: improving the therapeutic index. Blood, 126, 2452–2458.
- Kelly, K.M., Sposto, R., Hutchinson, R., Massey, V., McCarten, K., Perkins, S., Lones, M., Villaluna, D. & Weiner, M. (2011) BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group. Blood, 117, 2596–2603.
- Lister, T.A., Crowther, D., Sutcliffe, S.B., Glatstein, E., Canellos, G.P., Young, R.C., Rosenberg, S.A., Coltman, C.A. & Tubiana, M. (1989) Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. Journal of Clinical Oncology, 7, 1630–1636.
- Mauz-Korholz, C., Hasenclever, D., Dorffel, W., Ruschke, K., Pelz, T., Voigt, A., Stiefel, M., Winkler, M., Vilser, C., Dieckmann, K., Karlen, J., Bergstrasser, E., Fossa, A., Mann, G., Hummel, M., Klapper, W., Stein, H., Vordermark, D., Kluge, R. & Korholz, D. (2010) Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. Journal of Clinical Oncology, 28, 3680–3686.
- Press, O.W., Li, H., Schoder, H., Straus, D.J., Moskowitz, C.H., LeBlanc, M., Rimsza, L.M., Bartlett, N.L., Evens, A.M., Mittra, E.S., LaCasce, A.S., Sweetenham, J.W., Barr, P.M., Fanale, M.A., Knopp, M.V., Noy, A., Hsi, E.D., Cook, J.R., Lechowicz, M.J., Gascoyne, R.D., Leonard, J.P., Kahl, B.S., Cheson, B.D., Fisher, R.I. & Friedberg, J.W. (2016) 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. Journal of Clinical Oncology, 34, 2020–2027.
- Schwartz, C.L., Constine, L.S., Villaluna, D., London, W.B., Hutchison, R.E., Sposto, R., Lipshultz, S.E., Turner, C.S., deAlarcon, P.A. & Chauvenet, A. (2009) A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood, 114, 2051–2059.
- Straus, D.J., Jung, S.-H., Pitcher, B., Kostakoglu, L., Grecula, J.C., Hsi, E.D., Schöder, H., Popplewell, L.L., Chang, J.E. & Moskowitz, C.H. (2018) CALBG 50604: risk-adapted treatment of non-bulky early stage Hodgkin lymphoma based on interim PET. Blood, 132, 1013–1021.
- Trippett, T.M., Schwartz, C.L., Guillerman, R.P., Gamis, A.S., Gardner, S., Hogan, S., London, W.B., Chen, L. & de Alarcon, P. (2015) Ifosfamide and vinorelbine is an effective reinduction regimen in children with refractory/relapsed Hodgkin lymphoma, AHOD00P1: a children's oncology group report. Pediatric Blood & Cancer, 62, 60–64.
- Zinzani, P.L., Broccoli, A., Gioia, D.M., Castagnoli, A., Ciccone, G., Evangelista, A., Santoro, A., Ricardi, U., Bonfichi, M., Brusamolino, E., Rossi, G., Anastasia, A., Zaja, F., Vitolo, U., Pavone, V., Pulsoni, A., Rigacci, L., Gaidano, G., Stelitano, C., Salvi, F., Rusconi, C., Tani, M., Freilone, R., Pregno, P., Borsatti, E., Sacchetti, G.M., Argnani, L. & Levis, A. (2016) Interim positron emission tomography response-adapted therapy in advanced-stage Hodgkin lymphoma: final results of the phase II part of the HD0801 study. Journal of Clinical Oncology, 34, 1376–1385.