Page 37 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Interim PET as biomarker of response in HL and DLBCL?
Another important issue is whether early identification of patients who are likely to be refractory to R-CHOP will result in better outcomes if these patients can be salvaged with high-dose chemotherapy or novel non-chemotherapeutic agents. Progress in targeted therapies in DLBCL might shift treatment paradigms from broad-spectrum poly-chemotherapy towards more targeted therapies based on genetic heterogeneity and complexity. These new drugs are currently being tested within phase I-II trials and results are awaited. Predicting response or resistance to a specific therapy will not only expedite the introduction of the most effective therapy to the patient but will also most likely be necessary to reduce the overall costs.
Nowadays, international guidelines do not recommend changing standard treatment on iPET unless there is clear evidence of progression. Nonetheless, if mid-treatment imaging is performed, PET is better than CT at predicting prognosis and can be useful to exclude the possibility of progression. Preliminary published data and data presented only in abstract form suggest that, for patients with inadequate response on iPET, current chemotherapy-based escalation strategies may not overcome treatment resistance [19,23-24] (Table 1). For these patients, a more effective initial therapy regimen is needed.
Conclusions
FDG-PET is a reliable biomarker for assessing early response in HL. The high negative predictive value of CMR after 2-3 cycles of ABVD has been the basis for recent trials exploring de-escalation of therapy in early-stage disease. The high positive predictive value in advanced disease has also been the focus of clinical trials, with promising data presented for patients escalated from ABVD to BEACOPP if they do not achieve a CMR after 2 cycles. In HL, PET-adapted therapy based on early response is rapidly becoming a clinical reality.
In DLBCL, the ability to escalate treatment early for patients unlikely to respond to first-line immunochemotherapy is highly desirable, as these patients do not have good salvage options. Obtaining a CMR on interim PET has a high negative predictive value, but partial metabolic response is also often associated with good outcomes. Modifying treatment for patients who do not achieve an early CMR in DLBCL is likely to lead to overtreatment of a significant proportion of patients,
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