PET Scan Can Avoid Toxic Chemotherapy, Improve QoL

Treatments that do not impact outcomes but can cause severe side effects in patients should be avoided. Now, a new study in the New England Journal of Medicine has established that, at least in the case of lymphoma, a positron emission tomography (PET) scan can spare the patients serious side effects of chemotherapy.

The study, conducted among treatment-naïve patients diagnosed with advanced Hodgkin’s lymphoma, was conducted in Europe and in Australia. More than 1200 patients were scanned, at least 28 days prior to and following 2 cycles of standard chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine, also called ABVD). Patients with a clear PET scan (n = 935) were divided into 2 cohorts: 470 were assigned to continue on ABVD and 465 were assigned to receive chemotherapy without bleomycin (AVD). However, 10 patients did not receive the assigned therapy: 8 in the AVD group (2 elected to continue ABVD, 5 withdrew for other reasons, and 1 died before starting cycle 3) and 2 in the ABVD group.

At a median time of 41.2 months following the randomization, 142 events of disease progression, relapse, or death were observed, without a significant difference in the number of events in each group (HR with AVD, 1.13; 95% confidence interval [CI], 0.81-1.57; P = .48). The 3-year progression-free survival (PFS) rate was 85.7% (95% CI, 82.1-88.6) in the ABVD group and 84.4% (95% CI, 80.7-87.5) in the AVD group.

Patients who had a positive PET (n = 182) were administered the more aggressive treatment of escalated therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), with higher-than-standard doses of etoposide, doxorubicin, and cyclophosphamide. Of these, 94 received BEACOPP-14 (accelerated version with growth hormone support), 78 received escalated BEACOPP, 6 were withdrawn from the trial to undergo different salvage treatments, and 4 elected to continue ABVD. The 3-year PFS rate for the group as a whole was 67.5% (95% CI, 59.7-74.2), and the overall survival rate was 87.8% (95% CI, 81.5-92.1). Patients in both BEACOPP and BEACOPP-14 had similar outcomes and quite similar side effects.

Bleomycin has been an important drug to treat Hodgkin lymphoma for 30 years, but it has a potential risk of severe effects on the lungs—both short-term and long-term—with the risk of scarring that can lead to serious breathing problems.

Based on their results, the authors write that the inclusion of bleomycin in the first 2 cycles may still make a positive contribution to the control of Hodgkin’s lymphoma, but its omission after negative findings on an interim PET-CT scan carries a minimal risk of treatment failure. They emphasize that eliminating bleomycin reduced the occurrence of toxic effects in the AVD group: it lowered the incidence of fatigue and respiratory events and led to better preservation of the lung’s capacity to exclude carbon monoxide.

“Knowing which patients have a more difficult to treat form of the disease means we can select those who need stronger chemotherapy, while sparing everyone else the severe side effects such as infertility. This approach, along with a reduction in the need for radiotherapy, should substantially reduce damage to healthy tissues and the risk of second cancers caused by treatments,” said Peter Johnson, MD, from the University of Southampton, in a statement. Johnson led the study on behalf of Cancer Research UK.

Reference

Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med. 2016;374(25):2419-2429.