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Treatment cessation noninferior to radiation for PET-negative Hodgkin's lymphoma
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Patients with early-stage Hodgkin’s lymphoma who had negative PET findings after chemotherapy demonstrated comparable PFS whether they underwent consolidation radiation therapy or received no further treatment, according to study results.
“PET can be used to predict the prognosis in Hodgkin’s lymphoma, with a high negative predictive value associated with early metabolic response,” John Radford, MD, of the Institute of Cancer Sciences at the University of Manchester and the Christie NHS Foundation Trust, and colleagues wrote. “Therefore, this technique might be useful in guiding a response-adapted approach in early stage Hodgkin’s lymphoma, whereby patients who have positive PET findings after chemotherapy receive radiotherapy but patients with negative PET findings undergo no further treatment. The late toxic effects of radiotherapy are avoided in patients cured by chemotherapy and OS may be improved.”
John Radford
There has been uncertainty as to whether patients with early-stage Hodgkin’s lymphoma who have negative PET findings after three cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) benefit from radiotherapy, according to study background.
Radford and colleagues evaluated data from 602 patients newly diagnosed with stage IA (33.2%) or IIA Hodgkin’s lymphoma who received three ABVD chemotherapy cycles. The median age of the population was 34 years and 53.3% were male. Of the population, 571 underwent PET scanning, 426 of whom had negative PET findings.
Researchers then randomly assigned 420 patients with negative PET findings to involved-field radiotherapy (n = 209) or no further therapy (n = 211). All patients with positive PET findings (n = 145) received a fourth chemotherapy cycle followed by radiotherapy.
The trial assessed the noninferiority of no further treatment by excluding a difference in 3-year PFS of 7 or more percentage points. The interval from randomization to progression, relapse or death served as the primary endpoint. Secondary endpoints included the efficacy of PET scan positivity or negativity after chemotherapy, incidence of second cancers and OS.
Median follow-up was 60 months for patients with negative PET findings.
Overall, 90.5% (n = 380) of patients with negative PET findings were alive at follow-up without disease progression.
In the radiation cohort, eight patients experienced disease progression and eight patients died. Three of the patients who died had disease progression, and one death was related to Hodgkin’s lymphoma. Researchers noted that five of the patients who died from this cohort did not receive the assigned radiation therapy.
Twenty patients in the no therapy cohort experienced disease progression, and four patients died. Two of the patients who died had disease progression, although no deaths occurred due to their malignancy.
Three-year PFS rates from the intention-to-treat analysis were 94.6% (95% CI, 91.5-97.7) in the radiotherapy cohort and 90.8% (95% CI, 86.9-94.8) in the no further treatment cohort. The rate ratio for PFS favored radiotherapy (1.57; 95% CI, 0.84-2.97).
A majority of patients achieved 3-year OS in the radiotherapy group (97.1%; 95% CI, 94.8-99.4) and no treatment group (99%; 95% CI, 97.6-100) in the intention-to-treat analysis. The rate ratio favored no therapy (0.51; 95% CI, 0.15-1.68).
The per-protocol analysis (n = 392) yielded a 3-year PFS rates of 97.1% in patients who received radiotherapy and 90.8% in patients who received no further treatment. The rate ratio was 2.36 (95% CI, 1.13-4.95) in favor of radiotherapy (P = .02).
Of patients with positive PET findings, 87.6% (n = 127) were alive without disease progression at a median follow-up of 62 months. Ten patients experienced disease progression, and eight deaths occurred (five with disease progression).
“Although the noninferiority margin was exceeded in this study, the results suggest that radiotherapy can be avoided for patients with negative PET findings,” Radford and colleagues concluded. “A longer follow-up period is required to determine whether the response-adapted approach … leads to fewer second cancers, less cardiovascular disease and improved OS, as compared with a strategy incorporating radiotherapy for all patients.”
There are limitations to these findings that should be considered when interpreting the results, Dan L. Longo, MD, and James O. Armitage, MD, both of the division of hematology-oncology at the University of Nebraska Medical Center, wrote in an accompanying editorial.
“First, the patients did not undergo a baseline PET scan; thus, some patients may have actually had some more advanced disease,” Longo and Armitage wrote. “Second, the authors considered a score of 3 to indicate a positive PET finding — yet data from other studies suggest that in patients with Hodgkin’s and other lymphomas, scores of 2 or 3 are similar in outcome. Third, the key measure for efficacy is OS, and 5 years of follow-up is not sufficient to capture the treatment-related fatalities, which increase 10 to 30 years after treatment.”
Yet, based on these findings, the decision to undergo radiation therapy vs. no therapy after negative PET findings should involve the patient’s preferences, Longo and Armitage wrote.
“The patient should be involved in making that decision after being fully informed of the risks and the benefits,” they wrote. “Some patients will elect to receive additional therapy because they cannot live with the increased short-term risk of relapse. Others will elect to minimize the long-term risks and expect that they are among the 90% of patients who have already been cured by the chemotherapy.” – by Cameron Kelsall
Disclosure: Radford reports grant support from Leukemia and Lymphoma Research and the Lymphoma Research Trust, and personal fees from Teenage Cancer Trust during the conduct of the study. Armitage reports personal fees from Celgene, Coherus, Conatus, GlaxoSmithKline, Roche, Spectrum, Tesaro Inc. and Ziopharm. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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