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Stroke As a Late Treatment Effect of Hodgkin's Disease

Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands

Fiona Anne Stewart, Willem Boogerd

Division of Experimental Therapy and Department of Neuro-Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands

To the Editor:

Bowers et al¹ are commended for their large cohort study on the risk of stroke in long-term survivors of Hodgkin's disease. This is the first study showing an absolute increased risk of stroke in these young patients, who were not prone to atherosclerotic diseases because of their age. After a median interval of 17.5 years, these patients have an increased relative risk of stroke of 4.3 in comparison with a sibling control group. This observed increased risk is in agreement with the elevated risk of stroke we found in patients irradiated for head and neck tumors.² However, the interval before the onset of stroke is longer in the Hodgkin's population: 17.5 years versus 10.9 years in the head and neck population. This could possibly be explained by differences in underlying pathogenetic mechanisms. In atherosclerotic-naive patients, like in the Hodgkin's population, irradiation on the neck seems to induce atherosclerotic-like lesions of the carotid artery. In contrast, in the population of older patients with head and neck cancer, radiation therapy (RT) accelerates pre-existing atherosclerotic disease. Both processes can eventually cause stenosis of the carotid artery³ and thromboembolisms leading to stroke, but the timing of this depends on whether the atherosclerotic process was already initiated before irradiation. In addition, increased thickness of the carotid vascular wall in the older head and neck cancer patients might sooner induce flow disturbances and shear stress, further accelerating the atherosclerotic process. The relatively low-dose of RT used in the treatment of Hodgkin's disease (median dose, 40 Gy) compared with the dose used for head and neck cancer (60 to 70 Gy) might also contribute to slower progression of the lesions.

A limitation of the Bowers study is that stroke was not confirmed by a computed tomography scan. Therefore, the contribution of other causes of cerebrovascular disease, like intracranial hemorrhage, cannot be established, nor can the origin of stroke be ascertained. Hodgkin's disease patients who receive mantle irradiation are also at risk for cardiac disease, such as valvular diseases,⁴ which can also result in stroke in these patients.

We agree with the authors that patients who receive irradiation on the neck should be monitored, especially those patients who have an estimated long survival. However, the suggestion of interviewing patients to establish the occurrence of cerebrovascular disease is, in our view, not the most appropriate solution, because the damage has already been done by then. We suggest duplex screening of the carotid arteries as a crucial part of follow-up to identify damage before it is associated with clinical symptoms. The next step is to investigate possible intervention strategies in order to diminish these debilitating late complications in long-term survivors of cancer.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Bowers DC, McNeil DE, Liu Y, et al: Stroke as a late treatment effect of Hodgkin's Disease: A report from the Childhood Cancer Survivor Study. J Clin Oncol 23:6508-6515, 2005[Abstract/Free Full Text]

2. Dorresteijn LD, Kappelle AC, Boogerd W, et al: Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. J Clin Oncol 20:282-288, 2002[Abstract/Free Full Text]

3. Cheng SW, Ting AC, Lam LK, et al: Carotid stenosis after radiotherapy for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 126:517-521, 2000[Abstract/Free Full Text]

4. Hull MC, Morris CG, Pepine CJ, et al: Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy. JAMA 290:2831-2837, 2003[Abstract/Free Full Text]

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• In Reply:
  Daniel C. Bowers and Kevin C. Oeffinger
  JCO 2006 24: 1480-1481 [Full Text]

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