Hodgkin's Lymphoma: Stroke as Late Effect of Radiotherapy Reignites Question About Its Value

News Author: Zosia Chustecka
CME Author: Désirée Lie, MD, MSEd

June 23, 2009 — A new study showing that patients treated for Hodgkin's lymphoma have a substantially increased risk for stroke resulting from the radiation they received has again prompted questions about the value of radiotherapy in the treatment of this disease.

This has been a long-running debate, with opponents of radiotherapy arguing that it adds risk without clear benefit and that chemotherapy alone should be used in Hodgkin's lymphoma. In a hard-hitting editorial that accompanies the new study, Dan Longo, MD, from the National Institute on Aging in Baltimore, Maryland, says the persistent use of radiotherapy with chemotherapy in Hodgkin's disease "defies logical explanation."

We simply cannot keep exposing patients to risk without clear benefit.

"Given the life-long increased risks of late effects that have been documented from the use of radiation therapy, we simply cannot keep exposing patients to risk without clear benefit," he writes in his editorial published online June 17 in the Journal of the National Cancer Institute.

However, proponents of radiotherapy in Hodgkin's lymphoma argue that the outcomes with chemotherapy alone are inferior to those seen with both therapies, and point out that the current minifields of radiation used are less damaging than the older radiotherapy schedules.

Singling radiotherapy out as the source of all morbidity . . . [is] throwing the baby out with the bath water.

"Singling radiotherapy out as the source of all morbidity and replacing it with potentially worse or as-yet untested alternatives is taking the wrong route or throwing the baby out with the bath water," said Joachim Yahalom, MD, from Memorial Sloan-Kettering Cancer Center in New York City, an expert on radiotherapy in Hodgkin's disease who was approached for comment. He told Medscape Oncology that "Dr. Longo is notorious for his total and unselective opposition to using radiation."

Doubling of Risk for Stroke

The new study, also published online June 17 in the Journal of the National Cancer Institute, comes from the Netherlands. It involved 2201 patients with early-stage Hodgkin's lymphoma who were treated with either radiation or chemotherapy between 1965 and 1995 and who were followed for a median of 17.5 years. The event rate showed that, compared with the general population, these survivors have double the risk for stroke and triple the risk for transient ischemic attacks (TIAs).

Radiation to the neck and mediastinum was a statistically significant risk factor for the occurrence of ischemic stroke and TIA (P = .03), as was younger age on receiving radiotherapy and hypertension. However, chemotherapy did not increase this risk.

The authors, led by Marie De Bruin, MD, from the Department of Epidemiology at the Netherlands Cancer Institute in Amsterdam, conclude that in view of this increased risk for stroke and TIA, physicians seeing such patients should consider "appropriate risk-reducing strategies," such as hypertension and lifestyle changes. In the editorial, Dr. Longo adds hypercholesterolemia and smoking to that list.

However, Dr. Longo uses the results from this study to bolster his argument against the use of radiotherapy in Hodgkin's lymphoma. This latest quantification of yet another late adverse effect adds "to the already overwhelming evidence that the use of radiation therapy in Hodgkin's disease is shortsighted," he writes.

Balance Sheet of Risks vs Benefits

"These results should make an impact on the physician's choice of primary treatment," Dr. Longo writes. He then draws up a balance sheet of risks vs benefits.

Radiation therapy increases the risk for a second malignancy (1% per year, which does not decrease even 30 years after treatment), increases the risk for a myocardial infarction (3-fold), and now these latest data suggest it also increases the risk for an ischemic cerebrovascular event (2.5- to 3-fold), Dr. Longo points out.

"Those are the fatal risks," he notes. In addition, there are nuisance risks, like dental carries, dry mouth, dysgeusia, transverse myelitis, and hypothyroidism, that affect quality of life.

And what are the advantages? In Hodgkin's disease, the advantage of using radiotherapy is not clear at all, and indeed it could be argued that there is none, Dr. Longo writes. In fact, he has argued that there is none in a paper that he coauthored in a recent issue of the Cancer Journal (2009;15:150-154).

Dr. Longo disagrees. He told Medscape Oncology that the "literature is full of studies that demonstrate a small advantage for combined-modality therapy in remission duration (or disease-free or progression-free survival) early in the study that is completely erased by fatal toxicities associated with the use of radiation therapy, such that overall survival is either the same or favors chemotherapy alone."

There is no excuse for exposing patients to risk without benefits.

J Natl Cancer Inst. 2009;101:904-905, 928-937.(Abstract – szerk.)

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