PET-CT Better Than CT in Follicular Lymphoma

Alexander M. Castellino, PhD

September 18, 2014

Patients with follicular lymphoma generally respond well to initial treatment with immunochemotherapy, but relapse is common, and clinical outcomes are varied. At present, computed tomography (CT) is used routinely on patients when they receive their induction treatment, to ascertain the response to therapy and to predict survival.

New research shows that positron emission tomography (PET) CT is more accurate at predicting both progression-free survival (PFS) and overall survival (OS) in such patients, and researchers argue that it should become the new gold standard.

The results come from a pooled analysis of 3 trials and were published online September 18 in the Lancet Haematology to coincide with presentation at the 5th International Workshop on PET in Lymphoma in Menton, France.

Principal author Judith Trotman, MBChB, FRACP, FRCPA, of the Haematology Department at Concord Hospital, University of Sydney, Australia, emphasized the significance of these findings to Medscape Medical News.

"Our previous publications demonstrated the merits of postinduction PET-CT, but this study provides more robust data for OS and PFS with narrower confidence intervals," she said, "so clinicians now have better certainty in placing greater confidence in PET-CT over the preexisting standard of contrast-enhanced CT."

Dr. Trotman is confident that these data are poised to change clinical practice. "We expect this research will result in PET-CT imaging replacing CT, becoming the new gold standard to evaluate patients with follicular lymphoma," she said.

Indeed, PET-CT was recommended for follicular lymphoma in the recently published Revised Staging and Response Criteria, known as the Lugano Classification. Bruce D. Cheson, MD, of the Georgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC, authored an accompanying editorial. "These recommendations should make assessment of staging and response easier, and the fact that bone marrow biopsy is no longer required will be a welcome change for patients," he told Medscape Medical News.

Active Lymphoma "Lights Up" on Scan

In PET-CT, a radioactive tag (18F-fluorodeoxyglucose) is injected into the patient before he or she undergoes the CT scan. In patients with active lymphoma, the PET scan "lights up." The cancer is then graded on the new internationally accepted scoring system, the Deauville 5-point scale, in which a score of 4 or 5 is considered a positive scan after treatment.

Dr. Trotman and colleagues argue that this easily applied scale enables both researchers and practicing clinicians to establish prognosis for their lymphoma patients after first-line treatment, as well as after treatment for relapse.

There has been a suggestion that CT scanning should continue to be used in routine clinical practice, and that PET-CT scans be used only for patients whose results are unclear ― for example, in patients with incomplete or partial responses. However, Dr. Trotman and colleagues argue that this would mean that those patients receive 2 scans — adding to the cost, radiation exposure, anxiety, and inconvenience. In addition, there are a few patients who may be judged as complete responders with conventional CT and yet have positive results on PET-CT, and these patients would be missed, they point out.

The study results show that PET-CT has significantly higher predictive power than conventional CT in identifying lymphoma patients who are likely to relapse. The researchers say this information can be used to design the clinical follow-up for patients.

"Obtaining PET-negativity after therapy is reassuring for both patients and their clinicians, and predicts a prolonged remission," Dr Trotman told Medscape Medical News.

On the other hand, a positive postinduction scan "provides a platform for response-adapted therapy aimed to improve the poor prognosis of these patients, many of whom do not have indolent disease," she said.

Clinical Trials Used to Measure the Value of PET-CT

To link PET-CT to clinical outcomes, Dr. Trotman and colleagues collected imaging data from 3 prospective studies ― the PRIMA, PET-FL, and FOLL05. All 3 studies used both PET-CT and conventional CT to follow PFS and OS in patients receiving first-line or induction immunochemotherapy for advanced follicular lymphoma.

The study pooled available information from 246 patients whose scans reviewed centrally rather than at each center. Three blinded nuclear medicine physicians read baseline and postinduction scans of these patients. The postinduction scans were undertaken within 3 months following induction therapy.

The results show that a positive PET-CT scan after induction therapy was associated with worse clinical outcomes. The 4-year PFS rate for patients with a positive PET-CT scan was 23% vs 63% for patients with a negative PET-CT. Similarly, OS after 4 years was 87% for patients with a positive postinduction PET-CT compared with 97% for patients with a negative PET-CT.

In contrast, responses on conventional CT scans were weakly predictive of PFS (hazard ratio, 1.7; P = .017), the researchers note.

Readily Available Surrogate Endpoint

In the editorial, Dr. Cheson asks, "That patient outcome can be predicted with molecular imaging is good news: the question is, what should be done with this information?"

In clinical practice, patients with a positive scan should be followed up more closely, but there are no data as yet demonstrating that more intensive treatment leads to better outcomes, he point outs. He says that data from this study provide important research opportunities and that PET-CT may be used to improve patient outcomes in clinical studies. For example, he suggests that patients with a positive PET-CT can be randomly assigned either to receive treatment immediately or to defer treatment until disease progression.

"PET-CT provides a readily available surrogate endpoint with which to more rapidly develop better therapies for a population of patients with a predictably poor outcome," Dr. Cheson concluded in his commentary.

This study was funded by Groupe d’Etude des Lymphomes de l’Adulte (Paris, France), now LYSA (Lymphoma Study Association), Direction de la Recherche Clinique de l'Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Multiple authors have cited industry ties.

Lancet Haematol. Published online September 18, 2014. Abstract

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