Interim assessment and treatment adaptation
Interim FDG PET/CT (interim FDG PET/CT, or iPET) is usually performed after two cycles of chemotherapy. Studies have proven that this method predicts overall and progression-free survival more accurately than traditional computed tomography.
The main value of iPET is the possibility of response-adapted therapy. If the functional response is favorable, treatment can be safely de-escalated (e.g., omitting radiation therapy or toxic drugs such as bleomycin to reduce pulmonary toxicity). Conversely, if the interim scan is positive, treatment escalation is considered to improve prognosis.
The problem of residual masses
Even with successful treatment, enlarged lymph nodes do not always disappear completely. A residual mass of fibrous tissue often forms (especially in bulky initial disease — bulky disease).
- CT is unable to differentiate a scar from an active tumor based on density. Consequently, the method has low specificity.
- MRI helps differentiate tissues (the T2 signal of active tumor is high, whereas that of fibrosis is low), but small lesions may be missed, and inflammation frequently yields false-positive results.
- FDG PET/CT solves this problem due to its extremely high negative predictive value (NPV). A metabolically inactive lesion on PET is a reliable sign of remission.
Deauville scale and response criteria
To standardize PET/CT assessment, the Deauville criteria (Deauville criteria) are universally used. This is a visual scale in which radiopharmaceutical (FDG) uptake in lymphoma is compared with background uptake in the mediastinal blood pool and normal liver tissue:
- No uptake.
- Uptake ≤ mediastinum.
- Uptake > mediastinum, but ≤ liver.
- Uptake moderately higher than the liver.
- Uptake markedly higher than the liver (more than 3 times) or appearance of new lesions.
Within the Lugano classification, scores of 1, 2, and (most commonly) 3 indicate a complete metabolic response (complete metabolic response, CMR). Scores of 4 and 5 with decreased activity are regarded as a partial response, whereas increasing activity or the appearance of new lesions is considered progression.
Follow-up after completion of therapy
For patients who have achieved a complete response, routine surveillance imaging (surveillance imaging) has no evidence base.
In the absence of clinical symptoms of relapse, prophylactic PET/CT scans frequently lead to false-positive results (up to 20% of cases) due to inflammatory processes. This causes unnecessary anxiety and biopsies. Therefore, imaging is ordered only when there is clinical suspicion of relapse.
Briefly: answers to topical questions
What specific Lugano CT criteria are used to assess FDG-non-avid lymphomas?
Lugano CT criteria are used to assess lymphomas with low or variable FDG uptake.
- Complete Remission (Complete Remission) — complete disappearance of all radiologic evidence of disease; all lymph nodes have decreased to ≤ 1.5 cm in the longest transverse diameter.
- Partial Response (Partial Response) — in the presence of a residual mass, a partial response is recorded; the term "unconfirmed complete remission" is no longer used.
- Progression — appearance of any new extranodal lesion > 1 cm in any axis, new or recurrent splenomegaly (increase in spleen size by 50% over previous enlargement), new or definite progression of non-measurable lesions, appearance of a new lesion during or at the end of therapy.
- Rules for dividing/merging nodes: when a lesion divides, individual PPDs are summed; when nodes merge, the PPD of the confluent mass is measured, and an increase of more than 50% compared to the sum of PPDs of the individual nodes indicates progression.
What physiological and pathological processes cause false-positive FDG uptake after lymphoma treatment?
False-positive FDG uptake after lymphoma treatment may be associated with inflammatory and reactive processes.
- Inflammation — decreases the predictive value of a positive result, as inflammatory cells also take up FDG.
- Infection/inflammation — must be ruled out when new FDG-positive lesions appear; if uncertain, biopsy or repeat scanning should be considered.
- Reactive bone marrow hyperplasia — diffuse or heterogeneous radiopharmaceutical uptake may reflect reactive hyperplasia rather than infiltration, especially in Hodgkin lymphoma.
- Use of granulocyte colony-stimulating factors — reactive hyperplasia reduces the specificity of PET/CT, particularly if G-CSFs were administered.
To minimize inflammation-related false-positive results, post-treatment PET/CT should be performed no earlier than 6 weeks after the completion of chemotherapy.
In which Hodgkin lymphoma chemotherapy protocols is de-escalation based on interim PET/CT applied?
Therapy de-escalation based on interim PET/CT results is described in clinical trials for Hodgkin lymphoma.
- RAPID: patients with early-stage Hodgkin lymphoma and a negative iPET result after 3 cycles of ABVD chemotherapy can avoid radiation therapy.
- RATHL: patients with advanced-stage Hodgkin lymphoma and a complete metabolic response after 2 cycles of chemotherapy can safely omit bleomycin from subsequent cycles, reducing pulmonary toxicity.
In the event of a positive iPET result, the RATHL and H10 trials suggest that patients may have better outcomes with chemotherapy escalation from ABVD to BEACOPP.
How to remember the Deauville scale norm: anything that lights up on PET/CT less than or equal to the liver (scores 1–3) is a good response. If it lights up brighter than the liver (scores 4–5), it is active disease.
Class and exam questions
Why cannot a final PET/CT scan be performed immediately after the last chemotherapy infusion?
It is necessary to wait at least 6–8 weeks. Performing the scan too early can yield false-positive results due to nonspecific tissue inflammation following aggressive treatment.
What to do if PET/CT after therapy shows residual activity, but the patient feels well?
The positive predictive value (PPV) of functional imaging is not absolute, particularly in non-Hodgkin lymphomas after rituximab. In such cases, a biopsy of the most active lesion is strongly recommended prior to initiating salvage treatment (salvage treatment).
Is PET/CT used for all types of lymphomas?
The method replaces CT in routine evaluation only for FDG-avid lymphomas (Hodgkin lymphoma, aggressive B-cell NHLs). For lymphomas with low or variable FDG uptake, Lugano CT criteria are used.
What else to study on this topic
- Anatomic CT response criteria (Lugano) for non-FDG-avid lymphomas
- Rules for measuring lesions on CT: sum of the products of diameters (SPD) and perpendicular diameters (PPD)
- Escalation and de-escalation of therapy based on iPET results (analysis of RAPID and RATHL trials)
- Features of diffusion-weighted imaging (DWI) and ADC in MRI
- Indications and guidelines for image-guided biopsy in suspected relapse
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