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Annals of Oncology Advance Access published online on September 19, 2006
Annals of Oncology, doi:10.1093/annonc/mdl302
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© 2006 European Society for Medical Oncology
Received March 20, 2006
Revised July 3, 2006
Accepted July 11, 2006

original article

Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials

J. Franklin 1 *, A. Pluetschow 1, M. Paus 1, L. Specht 2, A.-P. Anselmo 3, A. Aviles 4, G. Biti 5, T. Bogatyreva 6, G. Bonadonna 7, C. Brillant 1, E. Cavalieri 3, V. Diehl 1, H. Eghbali 8, C. Fermé 9, M. Henry-Amar 10, R. Hoppe 11, S. Howard 12, R. Meyer 13, D. Niedzwiecki 14, S. Pavlovsky 15, J. Radford 16, J. Raemaekers 17, D. Ryder 16, P. Schiller 1, S. Shakhtarina 6, P. Valagussa 7, J. Wilimas 12, and J. Yahalom 18

1 German Hodgkin Study Group, University of Cologne, Germany
2 Rigshospitalet, Copenhagen, Denmark
3 University of La Sapienza, Rome, Italy
4 Oncology Hospital, National Medical Center, Mexico City, Mexico
5 University of Florence, Florence, Italy
6 Medical Radiological Research Centre, Obninsk, Russia
7 Istituto Nationale Tumore, Milan, Italy
8 Institut Bergonie, Bordeaux
9 Hopital Saint-Louis, Paris
10 Centre Regional Francoise Baclesse, Caen, France
11 Stanford University School of Medicine, Stanford, CA
12 St Judes Children's Research Hospital, Memphis, TN, USA
13 Hamilton Regional Cancer Center, Ontario, Canada
14 Duke University School of Medicine, Durham, NC, USA
15 FUNDALEU, Buenos Aires, Argentina
16 Christie Hospital, Manchester, UK
17 University Medical Center Nijmegen, Nijmegen, The Netherlands
18 Memorial Sloan-Kettering Cancer Center, New York, NY, USA

* To whom correspondence should be addressed.
J. Franklin, E-mail: jeremy.franklin{at}uk-koeln.de


  Abstract

Background: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial.

Patients and Methods: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method.

Results: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25).

Conclusions: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT.

Caution is needed in applying these findings to current therapies.

Keywords: chemotherapy; Hodgkin's lymphoma; meta-analysis; radiotherapy; second malignancies.
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