Edging closer to PET monitoring of therapy response in Hodgkin lymphoma

Personalized therapy assessment for Hodgkin lymphoma (HL) with interim FDG PET could help step up or step down treatment to find the curative sweet spot, but the transition from PET-adaptive clinical trials to practice requires additional time to prove broad benefit for patients, according to a review published July 1 in the Journal of Nuclear Medicine.

Lale Kostakoglu, MD, from the department of radiology division of nuclear medicine at Mount Sinai Medical Center in New York City, and colleagues collected literature on interim PET research and clinical trials using adaptive PET in the assessment of patients with HL to evaluate its effectiveness for tailoring treatments to each patient’s level of risk and response to therapy.

“Particularly, with the availability of various effective treatment regimens, there is a growing need for accurate prognostic surrogate markers to guide risk-adapted strategies to improve patient outcome by counterbalancing risk with benefit,” wrote the authors.

HL is curable with remission rates exceeding 75 percent in patients treated with standard ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), but 10 to 15 percent of early-stage and 20 to 30 percent of late-stage HL cases become progressive due to recurrent cancer and resistance to therapy. In addition to ABVD, escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, prednisone) is also emerging, although controversially, as a first-line therapy. ABVD with involved-field radiation therapy (IFRT) has been shown to lead to a progression-free disease state for approximately 80 percent of patients. But does the use of interim PET help to adapt treatment to individual patients’ needs for better outcomes and survival?

“F-18 FDG PET is a well-established surrogate for tumor chemosensitivity early during therapy,” wrote Kostakoglu et al. “The ongoing PET-adaptive clinical trials are testing the hypothesis that a decision can reliably be made on escalating or deescalating therapy based on interim PET results.”

After plumbing the studies, researchers found a few challenges. In the 25 percent of cases where interim PET did not lead to negative scan result, the imaging studies ran from obviously positive to weakly positive--10 to 15 percent of patients for the latter.

“Notably, minimal residual uptake in HL is usually caused by the inflammatory component of the tumor mass,” wrote the authors. “Consequently, interpreting the minimal residual uptake as negative would be clinically more appropriate to minimize false-positive results for residual disease.”

Some high false positives have been seen with PET/CT in limited stage HL and bulky masses were found to adversely impact specificity and positive predicive value of end-treatment. In one study of early-stage HL, PET scans following two series of standard treatments were found to be 13 percent positive in a subgoup with favorable prognosis and 23 percent positive for the unfavorable group. Another study revealed positive predictive values of 47 percent and 71 percent for post-second cycle bulky and nonbulky mass-bearing patients, respectively.

“The higher false-positive rates in bulky HL lesions could be based on a more pronounced inflammatory process within the tumor bulk, but tumor bulk is also an adverse prognostic factor for recurrence,” wrote the researchers.

The authors were left with a lot of unanswered questions that will require further research and additional clinical trials for answers about the overall benefit of interim PET for HL patients.

“The capability of a test to individualize treatment, either for escalation or deescalation of standard therapy, largely depends on its predictive power base on a priori definition of treatment response as well as improvement in patient outcomes,” the authors wrote. “Thus, the impact of a PET-adapted treatment strategy will be confirmed only after the outcome data prove the benefit of an effective therapeutic intervention over the standard approach. In this regard, the results of ongoing PET-adapted HL trials will play a major role in allowing PET/CT to claim a crucial role in individualizing HL treatment. However, until these results become available, treatment changes based on interim PET/CT results should be limited to clinical trial settings.”