Positron Emission Tomography–Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL): A Multicenter, Randomized Phase III Trial

Abstract

Purpose Interim positron emission tomography (PET) using the tracer, [F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP-plus rituximab (R-CHOP) in CD20-positive lymphomas-followed by a PET scan that was evaluated using the ΔSUV method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt's lymphoma protocol. PET-negative patients with CD20-positive lymphomas were randomly assigned or allocated to receive four additional cycles of R-CHOP or the same treatment with two additional doses rituximab. The primary end point was event-free survival time as assessed by log-rank test. Results Interim PET was positive in 108 (12.5%) and negative in 754 (87.5%) of 862 patients treated, with statistically significant differences in event-free survival and overall survival. Among PET-positive patients, 52 were randomly assigned to R-CHOP and 56 to the Burkitt protocol, with 2-year event-free survival rates of 42.0% (95% CI, 28.2% to 55.2%) and 31.6% (95% CI, 19.3% to 44.6%), respectively (hazard ratio, 1.501 [95% CI, 0.896 to 2.514]; P = .1229). The Burkitt protocol produced significantly more toxicity. Of 754 PET-negative patients, 255 underwent random assignment (129 to R-CHOP and 126 to R-CHOP with additional rituximab). Event-free survival rates were 76.4% (95% CI, 68.0% to 82.8%) and 73.5% (95% CI, 64.8% to 80.4%), respectively (hazard ratio, 1.048 [95% CI, 0.684 to 1.606]; P = .8305). Outcome prediction by PET was independent of the International Prognostic Index. Results in diffuse large B-cell lymphoma were similar to those in the total group. Conclusion Interim PET predicted survival in patients with aggressive lymphomas treated with R-CHOP. PET-based treatment intensification did not improve outcome.

Interim PET/CT based on visual and semiquantitative analysis predicts survival in patients with diffuse large B‐cell lymphoma

“…Increasing evidence has illustrated that the semiquantitative method using SUVmax reduction is more accurate than visual analysis, based on DS to identify subgroups of patients with significantly different prognoses. 6,[14][15][16][17] Our results are consistent with those of other studies and confirm that ΔSUVmax evaluation (cutoff value of 74%) of iPET/CT is an independent predictive factor for DLBCL patients. Survival analysis revealed that patients with ΔSUVmax ≥ 74% had a significantly better PFS and OS than did patients with ΔSUVmax < 74%, irrespective of DS scores (Figure 4).…”

“…Increasing evidence has illustrated that the semiquantitative method using SUVmax reduction is more accurate than visual analysis, based on DS to identify subgroups of patients with significantly different prognoses . Our results are consistent with those of other studies and confirm that ΔSUVmax evaluation (cutoff value of 74%) of iPET/CT is an independent predictive factor for DLBCL patients.…”

“…Several studies have demonstrated that patients who achieved a ΔSUVmax beyond the cutoff value on an iPET scan had favorable outcomes . Increasing evidence supports that ΔSUVmax seems better than DS when interpreting iPET results in DLBCL patients . However, iPET analysis needs further validation in clinical trials.…”

“…[12][13][14] Increasing evidence supports that ΔSUVmax seems better than DS when interpreting iPET results in DLBCL patients. 6,[14][15][16][17] However, iPET analysis needs further validation in clinical trials. Neither the DS nor the ΔSUVmax method considers the tumor burden during treatment.…”

Efficacy of the GMALL‐B‐ALL/NHL2002 protocol in Burkitt leukemia/lymphoma and aggressive non‐Hodgkin‐lymphomas with or without CNS involvement

“…The latter regimens are in use for more than a decade and produce excellent results in Burkitt lymphoma at the expense of considerable, nonetheless temporary toxicities . With regard to this toxicity and in light of the well‐documented failure of first‐line treatment intensification in unselected DLBCL patients, the efficacy of the BL‐type protocols has only been tested systematically in chemotherapy‐refractory DLBCL as determined by interim positron emission tomography (iPET) . Nevertheless, DLBCL as well as mantle cell lymphoma (MCL), B‐cell non‐Hodgkin lymphomas transformed from an indolent variant (tB‐NHL) and T‐cell non‐Hodgkin lymphomas (T‐NHL) sometimes present in a clinical constellation where (R)‐CHOP is considered inadequate.…”