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Long-term side effects after treatment of Hodgkin's lymphoma
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Long-term side effects associated with the treatment of Hodgkin’s lymphoma (HL) have frequently been reported during the last decades. Studies have shown increased mortality in HL survivors. Following Hodgkin’s lymphoma, second malignancies (SM) and cardiovascular disease (CVD) are the most common causes of death in individuals treated for HL. This study investigates the incidence of side effects such as SM, CVD and infections in a cohort diagnosed with HL in Sweden between 1965 and 1995. In addition, this study identifies covariate risk factors for late side effects in order to develop strategies that prevent morbidity and mortality in HL survivors.

Methods Using the Swedish Cancer Registry (SCR) at the National Board of Health and Welfare and the Multi-Generation Registry at Statistics (MGR) Sweden, we identified 6946 individuals diagnosed with HL between the years 1965 and 1995, and their first degree relatives (FDR) (n=17 858). In addition we identified the malignancies and inpatient care for CVD and infections for the HL cohort and their FDR. The standard incidence ratio (SIR) was calculated for the risk of SM, CVD and infections. For SM and CVD the risk also was stratified and calculated for family history of disease. The Swedish Hodgkin Intervention and Prevention study (SHIP), a prospective study, invited 702 individuals treated for HL at the age of 45 years or younger and who were treated in the region of Skåne, Uppsala or Umeå. The participants completed a questionnaire and were invited to an out-patient visit to an oncologist with clinical examination and blood tests. Any pathological findings were referred for further investigation.

Results An increased risk for SM in HL long-term survivors was observed and seems to increase with the number of FDRs with cancer. There was also an increased risk for inpatient care due to congestive heart failure (CHF) and coronary artery disease (CAD). A family history of CHF and CAD further increased the risk for these diseases. The risk for inpatient care due to infections was increased and remained increased after 20 years or longer. The risk for infections was associated with splenectomy and hypothyroidism. Radiotherapy was an independent risk factor for cardiovascular disease in the cohort of the prospective study.

ConclusionLong-term survivors from HL have an increased risk for developing late side effects such as SM, CVD and infections. Since many HL patients are young and the cure rate from the disease is high, it is of great importance to offer focused surveillance programs to selected individuals who are at high risk, e.g. individuals who received radiotherapy as part of their treatment and who have other known risk factors for cardiovascular disease such as hypertension, hypercholesterolemia, family history and smoking.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2011. , 46 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1416
Keyword [en]
Hodgkin, survivorship, long-term side effects, cardiovascular disease, second malignancy, infections, prevention
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:umu:diva-43287ISBN: 978-91-7459-188-0OAI: oai:DiVA.org:umu-43287DiVA: diva2:412776
Public defence
2011-05-20, Bergasalen, By 27, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-04-29 Created: 2011-04-26 Last updated: 2011-04-29Bibliographically approved
List of papers
1. Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma
Open this publication in new window or tab >>Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma
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2008 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 98, no 5, 1001-1005 p.Article in journal (Refereed) Published
Abstract [en]

This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965–1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or ≥2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme.

Keyword
late effect, radiotherapy, second malignancy, cohort
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-9247 (URN)10.1038/sj.bjc.6604244 (DOI)18268493 (PubMedID)
Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2011-04-29Bibliographically approved
2. Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors: retrospective cohort analyses and a concept for prospective intervention
Open this publication in new window or tab >>Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors: retrospective cohort analyses and a concept for prospective intervention
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2009 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, no 8, 1914-1917 p.Article in journal (Refereed) Published
Abstract [en]

Previous studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first-degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in-patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in-patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow-up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on-going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept.

Keyword
Hodgkin; survivorship; cardiovascular disease; prevention
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-20631 (URN)10.1002/ijc.24147 (DOI)19165857 (PubMedID)
Available from: 2009-03-24 Created: 2009-03-24 Last updated: 2011-04-29Bibliographically approved
3. Long term risk of infections in Hodgkin lymphoma long-term survivors
Open this publication in new window or tab >>Long term risk of infections in Hodgkin lymphoma long-term survivors
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2011 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 154, no 5, 661-663 p.Article in journal (Refereed) Published
Keyword
survivorship, Hodgkin lymphoma, late effects, cohort, infection
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-42686 (URN)10.1111/j.1365-2141.2011.08638.x (DOI)21470197 (PubMedID)
Available from: 2011-04-12 Created: 2011-04-12 Last updated: 2011-09-29Bibliographically approved
4. Cardiovascular side effects following treatment of Hodgkin’s lymphoma: comorbidity factors and a strategy for intervention
Open this publication in new window or tab >>Cardiovascular side effects following treatment of Hodgkin’s lymphoma: comorbidity factors and a strategy for intervention
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(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-43271 (URN)
Available from: 2011-04-26 Created: 2011-04-26 Last updated: 2011-04-29Bibliographically approved

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