Abstract
INTRODUCTION
A cohort study from the United States showed that Hodgkin Lymphoma patients in the SEER database had more than two times the risk of suicide compared to the general US population (J Clin Oncol 2008 26:4731-38). However, the risk of suicide in Hodgkin Lymphoma has not been studied in European clinical trial patients where treatment and disease specific information was available.
METHODS
Patients from the German Hodgkin Study Group (GHSG) HD7 through HD15 studies were analyzed to identify those patients with Hodgkin Lymphoma whose cause of death was suicide. 12,201 patients from Germany, Switzerland, the Netherlands, the Czech Republic, and Austria were included in the analysis of the GHSG HD7-HD15 studies between 1993 and 2009. Median follow-up in these studies was 67.6 months or 5.63 years. Standardized mortality ratio (SMR) for death from suicide was calculated using the general European population as a control. Suicide as a cause of death was compared to other causes of death in the HD7-HD15 studies. Data from other European HL studies was planned to be included but not available at time of submission.
RESULTS
19 patients (17 males and 2 females) died by suicide in the HD7-HD15 studies during a total observation time of 68,638 person-years, equivalent to 27.7/100,000 person-years. When compared to the suicide rate in the general European population of 12.3/100,000 person-years (Eurostat Statistics Database 2010), the standardized mortality ratio (SMR) in this cohort was 2.25 (95% CI, 1.40 to 3.45) and statistically significant (p=0.0017).
Male gender is an established risk factor for suicide in the general population. Male and female suicide rates in the general European population were 20.7/100,000 and 4.7/100,000 person-years (Eurostat 2010) respectively. Male European HD7-HD15 patients had a suicide rate of 43.9/100,000 person-years with a SMR 2.12 (95% CI, 1.28 to 3.33), p=0.0054. Female European HD7-HD15 clinical trial patients had a suicide rate of 6.7/100,000 person-years with a SMR 1.43 (95% CI, 0.24 to 4.72), p=0.575.
Median age at diagnosis was 38 years (range 19-59) for the HL patients with suicide. Median time interval between diagnosis of HL and suicide was 42 months (range 1-142), and median age at time of suicide was 46 years (range 22-59). Nodular sclerosis (58%) and mixed cellularity (26%) were the most common HL histologic subtypes in patients with suicide. As defined by the GHSG, advanced stage HL (42%) was the most common in suicide followed by early stage favorable (37%) and early stage unfavorable (21%).
74% of HL patients with suicide received radiation therapy at a median dose of 30 Gy, with 58% receiving involved-field radiation therapy (IFRT) and 16% extended-field radiation therapy (EFRT). All patients with suicide received chemotherapy (median 4 cycles), with ABVD (32%), COPP/ABVD (16%), escalated-dose BEACOPP (16%), and escalated-dose followed by baseline-dose BEACOPP (16%) as the most common regimens.
17 of 19 patients (90%) were in remission with no evidence of progression or relapsed HL at time of suicide. One patient developed a secondary malignancy (melanoma) prior to death from suicide. There were a total of 818 deaths (6.7%) in the 12,201 patients analyzed in the HD7-HD15 studies. Suicide (2.3%) was the fifth most common cause of death after Hodgkin Lymphoma (29.6%), toxicity from treatment (primary, salvage, and infection = 24.8%), secondary malignancy (21.1%), and cardiopulmonary causes (10.1%). Figure 1.
CONCLUSIONS
Hodgkin Lymphoma patients treated within clinical trials in Europe have greater than twice the incidence of suicide, SMR 2.25, compared to the general population. This is similar to the SMR 2.07 reported in HL patients from the SEER database in the United States. This increase in suicide incidence is in spite of the excellent prognosis in HL, as evidenced by the 90% of patients who were in remission at time of suicide. Male European HL clinical trial patients had over twice the risk of suicide compared to males in the general population, but there was no statistically significant difference found in female European HL patients. With HL occurring most frequently in age groups with a high risk of suicide, clinicians must be vigilant about suicide as a significant cause of death in these patients.
Causes of Mortality in HD7-HD15 studies.
Engert:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. LaCasce:Seattle Genetics: Research Funding; Forty Seven Inc.: Consultancy.
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