PET can spare Hodgkin's lymphoma patients from undergoing RT after chemotherapy

A recent study in The New England Journal of Medicine suggests that FDG-PET after three cycles of chemotherapy can prevent patients with early-stage Hodgkin’s lymphoma from undergoing subsequent radiotherapy.

In discussing the trial, John Radford, MD, University of Manchester, and colleagues observed that patients with stage IA or stage IIA Hodgkin’s lymphoma are commonly exposed to 20 Gy of involved-field radiotherapy after being treated with two cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy.

Since PET findings can be used to predict a prognosis in Hodgkin’s lymphoma, they wanted to know if physicians could use PET scanning to avoid exposing patients to subsequent radiotherapy and its known side effects—“hypothyroidism, second cancers (especially of the breast and lung), and cardiovascular disease”—if chemotherapy cured the patient on its own.

“In moving toward the goal of maximizing cure while minimizing toxic effects, greater individualization of therapy is appealing,” Radford et al wrote. “This technique might be useful in guiding a response-adapted approach in early-stage Hodgkin’s lymphoma …the late toxic effects of radiotherapy are avoided in patients cured by chemotherapy, and overall survival may be improved.”

The Randomized Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease (RAPID) trial ran from October 2003 to August 2010. 571 patients with newly-diagnosed stage IA or stage IIA Hodgkin’s lymphoma went through three cycles of ABVD chemotherapy. A PET scan was then performed during the two weeks after day 15 of the third cycle. Patients with negative PET findings would be randomly assigned to either receive radiotherapy or receive no further treatments. (Patients with positive PET findings received more chemotherapy and the the common practice of involved-field radiotherapy.)

420 total patients with negative PET findings were randomly split into the two test groups. 211 patients had no further therapy, and 209 patients had the commonly-prescribed dose of radiology.

More than three years after the final patient underwent randomization, 380 (90.5%) of the patients with negative PET findings were alive without disease progression. 187 (88.6%) of the patients who received no further treatment were alive without disease progression, and 193 (92.3%) of the patients who received radiotherapy were alive without disease progression. While slightly more patients who received radiotherapy were alive without disease progression than those who received no further treatment, the authors observed that one must consider the importance of avoiding radiotherapy’s side effects when reviewing the numbers.

“These results … show that a modest improvement in the 3-year progression-free survival rate can be obtained with the addition of radiotherapy,” Radford et all wrote. “However, this effect is bought at the expense of exposing all patients to radiation, most of whom will not benefit and some of whom will be harmed. In fact, for patients cured with chemotherapy, the addition of radiotherapy can only contribute additional toxic effects.”

The authors note that results were not conclusive, and that a longer follow-up period is required to determine if limiting radiotherapy to patients with negative PET findings will lead to “fewer second cancers, less cardiovascular disease and improved overall survival.”