Originally published as JCO Early Release 10.1200/JCO.2003.07.131 on July 28 2003
Journal of Clinical Oncology, Vol 21, Issue 18
(September), 2003: 3431-3439
© 2003 American Society for Clinical Oncology
Long-Term Cause-Specific Mortality of Patients Treated for Hodgkins Disease
Berthe M.P. Aleman,
Alexandra W. van den Belt-Dusebout,
Willem J. Klokman,
Mars B. vant Veer,
Harry Bartelink,
Flora E. van Leeuwen
From the Department of Radiotherapy, and the Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam; and the Department of Hematology, the Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands.
Address reprint requests to Flora E. van Leeuwen, PhD, Department of Epidemiology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; e-mail: f.v.leeuwen{at}nki.nl.
Purpose: To assess long-term cause-specific mortality of young Hodgkins disease (HD) patients.
Patients and Methods: The study population consisted of 1,261 patients treated for HD before age 41 between 1965 and 1987. Follow-up was complete until October 2000. For 95% of deaths, the cause was known. Long-term cause-specific mortality was compared with general population rates to assess relative risk (RR) and absolute excess risk (AER) of death.
Results: After a median follow-up of 17.8 years, 534 patients had died (55% of HD). The RR of death from all causes other than HD was 6.8 times that of the general population, and still amounted to 5.1 after more than 30 years. RRs of death resulting from solid tumors (STs) and cardiovascular disease (CVD) were increased overall (RR = 6.6 and 6.3, respectively), but especially in patients treated before age 21 (RR = 14.8 and 13.6, respectively). When these patients grew older, this elevated mortality decreased. The overall AER of death from causes other than HD increased throughout follow-up. Patients receiving salvage chemotherapy had a significantly increased RR of death from STs, compared to patients receiving initial therapy only.
Conclusion: The main cause of death among HD patients was lymphoma, but after 20 years, HD mortality was negligible. The RRs and AERs of death from second primary cancers (SCs) and CVDs continued to increase after 10 years. Even more than 30 years after diagnosis, HD patients experienced elevated risk of death from all causes other than HD. Increased risk of death from SCs and CVDs was found especially in patients treated before age 21, but these risks seemed to abate with age.
Supported by Dutch Cancer Society grant NKI 98-1833.
This article has been cited by other articles:

|
 |

|
 |
 
A. Re, S. Ferrari, P. Frata, C. Pizzocaro, C. Crippa, A. Tucci, F. Facchetti, L. Grazioli, S.M. Magrini, and G. Rossi
Late computed tomography scan response improvement and gallium scintigraphy evaluation as on-treatment prognostic parameters to tailor treatment intensity in patients with Hodgkin's lymphoma. A prospective phase II study
Ann. Onc.,
May 1, 2008;
19(5):
951 - 957.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. K. Ng
Second Cancers after Hodgkin's Lymphoma: Long-term Risks
ASCO Educational Book,
January 1, 2008;
2008(1):
418 - 422.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. De Bruin, J. Huisbrink, M. Hauptmann, M. A. Kuenen, G. M. Ouwens, M. B. van't Veer, B. M. P. Aleman, and F. E. van Leeuwen
Treatment-related risk factors for premature menopause following Hodgkin lymphoma
Blood,
January 1, 2008;
111(1):
101 - 108.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. C. Hodgson, E. S. Gilbert, G. M. Dores, S. J. Schonfeld, C. F. Lynch, H. Storm, P. Hall, F. Langmark, E. Pukkala, M. Andersson, et al.
Long-Term Solid Cancer Risk Among 5-Year Survivors of Hodgkin's Lymphoma
J. Clin. Oncol.,
April 20, 2007;
25(12):
1489 - 1497.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Senan and E. F. Smit
Design of Clinical Trials of Radiation Combined with Antiangiogenic Therapy
Oncologist,
April 1, 2007;
12(4):
465 - 477.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. M. P. Aleman, A. W. van den Belt-Dusebout, M. L. De Bruin, M. B. van 't Veer, M. H. A. Baaijens, J. P. d. Boer, A. A. M. Hart, W. J. Klokman, M. A. Kuenen, G. M. Ouwens, et al.
Late cardiotoxicity after treatment for Hodgkin lymphoma
Blood,
March 1, 2007;
109(5):
1878 - 1886.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Swerdlow, C. D. Higgins, P. Smith, D. Cunningham, B. W. Hancock, A. Horwich, P. J. Hoskin, A. Lister, J. A. Radford, A. Z. S. Rohatiner, et al.
Myocardial Infarction Mortality Risk After Treatment for Hodgkin Disease: A Collaborative British Cohort Study
J Natl Cancer Inst,
February 7, 2007;
99(3):
206 - 214.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. B. Travis
Evaluation of the Risk of Therapy-Associated Complications in Survivors of Hodgkin Lymphoma
Hematology,
January 1, 2007;
2007(1):
192 - 196.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Ng and P. Mauch
The impact of treatment on the risk of second malignancy after Hodgkin's disease
Ann. Onc.,
December 1, 2006;
17(12):
1727 - 1729.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Brusamolino, A. Baio, E. Orlandi, L. Arcaini, F. Passamonti, V. Griva, W. Casagrande, C. Pascutto, P. Franchini, and M. Lazzarino
Long-term Events in Adult Patients with Clinical Stage IA-IIA Nonbulky Hodgkin's Lymphoma Treated with Four Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Adjuvant Radiotherapy: A Single-Institution 15-Year Follow-up.
Clin. Cancer Res.,
November 1, 2006;
12(21):
6487 - 6493.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Carde
In Reply
J. Clin. Oncol.,
July 10, 2006;
24(20):
3309 - 3310.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. M. Noordijk, P. Carde, N. Dupouy, A. Hagenbeek, A. D.G. Krol, J. C. Kluin-Nelemans, U. Tirelli, M. Monconduit, J. Thomas, H. Eghbali, et al.
Combined-Modality Therapy for Clinical Stage I or II Hodgkin's Lymphoma: Long-Term Results of the European Organisation for Research and Treatment of Cancer H7 Randomized Controlled Trials
J. Clin. Oncol.,
July 1, 2006;
24(19):
3128 - 3135.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Ferme, N. Mounier, O. Casasnovas, P. Brice, M. Divine, A. Sonet, F. Bouafia, A. Bastard-Stamatoullas, D. Bordessoule, L. Voillat, et al.
Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte (GELA)
Blood,
June 15, 2006;
107(12):
4636 - 4642.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. F. Koontz, J. P. Kirkpatrick, R. W. Clough, R. G. Prosnitz, J. P. Gockerman, J. O. Moore, and L. R. Prosnitz
Combined-Modality Therapy Versus Radiotherapy Alone for Treatment of Early-Stage Hodgkin's Disease: Cure Balanced Against Complications
J. Clin. Oncol.,
February 1, 2006;
24(4):
605 - 611.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. A. Stewart, S. Heeneman, J. te Poele, J. Kruse, N. S. Russell, M. Gijbels, and M. Daemen
Ionizing Radiation Accelerates the Development of Atherosclerotic Lesions in ApoE-/- Mice and Predisposes to an Inflammatory Plaque Phenotype Prone to Hemorrhage
Am. J. Pathol.,
February 1, 2006;
168(2):
649 - 658.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. B. Travis, C. S. Rabkin, L. M. Brown, J. M. Allan, B. P. Alter, C. B. Ambrosone, C. B. Begg, N. Caporaso, S. Chanock, A. DeMichele, et al.
Cancer Survivorship--Genetic Susceptibility and Second Primary Cancers: Research Strategies and Recommendations
J Natl Cancer Inst,
January 4, 2006;
98(1):
15 - 25.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. J. Savage, N. Al-Rajhi, N. Voss, C. Paltiel, R. Klasa, R. D. Gascoyne, and J. M. Connors
Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience
Ann. Onc.,
January 1, 2006;
17(1):
123 - 130.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. B. Travis, D. Hill, G. M. Dores, M. Gospodarowicz, F. E. van Leeuwen, E. Holowaty, B. Glimelius, M. Andersson, E. Pukkala, C. F. Lynch, et al.
Cumulative Absolute Breast Cancer Risk for Young Women Treated for Hodgkin Lymphoma
J Natl Cancer Inst,
October 5, 2005;
97(19):
1428 - 1437.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Hjermstad, S. D. Fossa, L. Oldervoll, H. Holte, A. B. Jacobsen, and J. H. Loge
Fatigue in Long-Term Hodgkin's Disease Survivors: A Follow-Up Study
J. Clin. Oncol.,
September 20, 2005;
23(27):
6587 - 6595.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Connors
State-of-the-Art Therapeutics: Hodgkin's Lymphoma
J. Clin. Oncol.,
September 10, 2005;
23(26):
6400 - 6408.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. C. Lavoie, J. M. Connors, G. L. Phillips, D. E. Reece, M. J. Barnett, D. L. Forrest, R. D. Gascoyne, D. E. Hogge, S. H. Nantel, J. D. Shepherd, et al.
High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver
Blood,
August 15, 2005;
106(4):
1473 - 1478.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. M. Meyer, M. K. Gospodarowicz, J. M. Connors, R. G. Pearcey, A. Bezjak, W. A. Wells, B. F. Burns, J. N. Winter, S. J. Horning, A. R. Dar, et al.
Randomized Comparison of ABVD Chemotherapy With a Strategy That Includes Radiation Therapy in Patients With Limited-Stage Hodgkin's Lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group
J. Clin. Oncol.,
July 20, 2005;
23(21):
4634 - 4642.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. P. Canellos
Chemotherapy Alone for Early Hodgkin's Lymphoma: An Emerging Option
J. Clin. Oncol.,
July 20, 2005;
23(21):
4574 - 4576.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Re, R. K. Thomas, K. Behringer, and V. Diehl
From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic potential
Blood,
June 15, 2005;
105(12):
4553 - 4560.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Connors
Evolving Approaches to Primary Treatment of Hodgkin Lymphoma
Hematology,
January 1, 2005;
2005(1):
239 - 244.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Rueda Dominguez, A. Marquez, J. Guma, M. Llanos, J. Herrero, M. A. de las Nieves, J. Miramon, and E. Alba
Treatment of stage I and II Hodgkin's lymphoma with ABVD chemotherapy: results after 7 years of a prospective study
Ann. Onc.,
December 1, 2004;
15(12):
1798 - 1804.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Feugier, E. Labouyrie, M. Djeridane, A. Jenabian, V. Dubruille, C. Berthou, C. Ghandour, B. Desablens, Y. Chait, P. Casassus, et al.
Comparison of initial characteristics and long-term outcome of patients with lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma at clinical stages IA and IIA prospectively treated by brief anthracycline-based chemotherapies plus extended high-dose irradiation
Blood,
November 1, 2004;
104(9):
2675 - 2681.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Behringer, A. Josting, P. Schiller, H. T. Eich, H. Bredenfeld, V. Diehl, and A. Engert
Solid tumors in patients treated for Hodgkin's disease: a report from the German Hodgkin Lymphoma Study Group
Ann. Onc.,
July 1, 2004;
15(7):
1079 - 1085.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. M. P. Aleman, N. S. Russell, H. Bartelink, and F. E. van Leeuwen
Re: Radiation Therapy in the Treatment of Hodgkin's Disease--Do You See What I See?
J Natl Cancer Inst,
February 4, 2004;
96(3):
235 - 236.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Diehl
Chemotherapy or Combined Modality Treatment: The Optimal Treatment for Hodgkin's Disease
J. Clin. Oncol.,
January 1, 2004;
22(1):
15 - 18.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Connors
Hodgkin's Lymphoma: The Hazards of Success
J. Clin. Oncol.,
September 15, 2003;
21(18):
3388 - 3390.
[Full Text]
[PDF]
|
 |
|
|