Both metastases and primary malignancies are commonly seen in the liver. As liver involvement is effective on survival, early detection of response has a crucial role in patient management (2-5). After LRTs such as TARE and TACE, there is no standard response evaluation and follow-up protocol; valuation is performed at different times with PET / CT, CT, or MR, depending on the center's practice and patient management. Since response assessment with CT and MRI takes a longer time and have their limitations, PET, a functional and molecular imaging technique, is used for early response evaluation with agents that reflect tumor-specific metabolism. Providing metabolic and anatomical information, PET / CT, and PET / MR have become the leading imaging techniques in cancer patient management [12-22].
F18-FDG PET / CT is the most common metabolic imaging method in diagnosing, staging, restaging and evaluating the treatment response due to increased glucose metabolism in many types of cancer. F18-FDG PET-CT can be used to assess treatment response in poorly differentiated and high-grade tumors. However, since small and well-differentiated tumors (such as HCC, NET) shows low or no FDG uptake due to low glucose metabolism and cellularity, imaging with new tumor-specific agents is needed [17-22,25-27]. PET / CT imaging with F18-FLT reflects cells' proliferation, is a non-invasive method in a personalized treatment approach [25-27].
In addition to complex and competing factors in the FLT uptake mechanism, there are notable differences between patient preparation, imaging time after injection, protocol, amount of injected activity, reconstruction method, timing before and after treatment, and patient numbers in studies withF18-FLT PET / CT. The power of studies is weak, as the number of patients achieving all the treatments and an ideal comparison in different disease groups is limited. It is noteworthy that data and various analysis techniques, such as semi-quantitative or visual evaluation are used [22-30]. Considering all the factors mentioned above are influential in the response evaluation, and there is no standard protocol, it is difficult to compare the studies.
As far as it is known, this is the first study to investigate the place of F18-FLT PET / CT in the early evaluation after TARE. Mogensen et al. investigated F18-FLT PET/CT's role in patients with at least one measurable (> 1 cm) colorectal cancer liver metastasis and received first-line chemotherapy. They reported a reduction in F18-FLT uptake in 23 patients (85%), whereas there was no relationship between the early change in measured F18-FLT SUVmax, and RECIST 1.1 based response (p = 0.24) . There was no relationship between ΔSUVmax, ΔSUVmean, and ΔSUVpeak values and RECIST 1.1 and PERCIST based responses in this current study. However, there was a significant relationship between PFS for target lobe and change in SUVmax and SUVpeak values.
Contractor K. et al. investigated F18-FLT PET/CT's role in evaluating the treatment response of breast and colorectal cancer liver metastases. They reported that 26/33 metastases were visible after kinetic spatial filtering (FLT-PETKSF). FLT-PET SUVave or SUVmax and FLT-PETKSF showed a significant decrease in responders two weeks after the first-line chemotherapy. It has been reported that the change in FLT can distinguish those who responded to the treatment with 83% sensitivity and 78% specificity from non-responders . In this current study, F18-FDG and F18-FLT PET / CT were evaluated for the treatment response after TARE, an LRT, not a systemic treatment. There was no significant correlation between ΔSUVmax, ΔSUVmean, and ΔSUVpeak values among the patients with and without response; therefore, sensitivity and specificity could not be calculated.
The critical point in the early evaluation of the treatment response is to distinguish non-responder to discontinue unnecessary treatment, thus avoid toxicity and cost. It is essential to determine the resectable disease from those that require more aggressive treatment. Patients with shrinkage of tumors up to 30% are considered to have stable disease, according to RECIST 1.1, and unresponsive to treatment [12-17]. In this study, tumor sizes of patients with stable disease decreased, reflecting the beneficial effect of treatment. However, since this decrease in size remained below the RECIST 1.1 criteria, it was accepted as a stable disease and unresponsive to treatment. It should be recognized that patients with stable disease, especially with colon cancer, are admitted as responders and continue to receive systemic therapy in clinical practice . Generally, chemotherapy-refractory liver metastases are referred for LRTs such as TARE. Thus, even defined stable disease can provide more prolonged survival and can be accepted as responsive. If patients with stable disease are admitted as responders to therapy, statistical analysis can be found significant in long-term follow-up results. Since there was no increase in the F18-FLT uptake after treatment in any of the patients, it could not be evaluated whether this was related to progressive disease. Since the tumors were hypometabolic in most patients, the changes in the F18-FLT SUVmax, SUVmean, and SUVpeak values were not significantly different in responder and non-responder patients. Since liver resection was not performed on any of the patients after embolization, except for the transplantation patient, post-treatment histopathological tumor changes and correlation with F18-FLT values could not be evaluated.
The most significant limitation of this study is the small sample size, consequent heterogeneous patient population, and the small number of patients who responded to the therapy. Therefore, in statistical analysis, results reaching a significant degree could not be obtained in SUV parameters. TARE candidate patients have many different clinical scenarios such as highly variable liver lesion number and size, disease stage, history of single or multi-step systemic treatment, liver resection, transplant, and LRT's. Also, since there is a clear difference in disease etiologies, current clinical and radiological status, it was impossible to standardize the patient group. Further studies with larger and standardized patient populations are needed.
It can be argued that the timing of the F18-FLT was not right. TARE is an internal radiotherapy procedure, and response to radiotherapy is generally evaluated later than chemotherapy/ selective systemic therapies [25,26]. F18-FDG PET/CT and F18-FLT PET/CT imaging were done ≥4 weeks after the procedure. Studies evaluating radiotherapy response revealed a significant relationship between F18-FLT PET/CT and response or survival in patients with head-neck, esophageal, breast, lung, rectal, etc. cancer . This study aimed to distinguish real responders from non-responders who were grouped based on post-radiotherapy response assessment techniques F18-FDG PET/CT and CT or MR. No correlation was found between the semi-quantitative values such as ΔSUVmax, ΔSUVmean, ΔSUVpeak, SUVmaxTBR, SUVmeanTBR, and SUVpeakTBR values calculated from F18-FLT PET / CT images. There was a significant relationship between OS and ΔSUVmax, and ΔSUVpeak values only when >30% change accepted as significant.