Factors Influencing Biochemical Progression in Distant Metastatic Papillary Thyroid Carcinoma

Background In advanced papillary thyroid carcinoma (PTC), particularly distant metastatic PTC (DM-PTC), disease progression is primarily monitored through serum markers like thyroglobulin (Tg) and imaging modalities such as computed tomography (CT). Due to limitations inherent in imaging techniques, such as radiation exposure, high cost, and complexity of metastatic lesion distribution, Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) often fail to timely capture disease changes in DM-PTC patients. The integration of Tg doubling time (TgDT) has demonstrated its efficacy in sensitively monitoring PTC disease progression. Objective To explore the biochemical progression and its influencing factors in DM-PTC using TgDT as the outcome variable. Methods This retrospective study included 61 DM-PTC patients treated at the Department of Nuclear Medicine, Peking Union Medical College Hospital from January 2018 to June 2023. Baseline data and genetic mutation analyses (including BRAF mutation, TERT mutation, RET fusion, and RAS mutation) were collected. Peripheral blood T cell subsets, natural killer (NK) cells, and lymphocyte counts were measured 4 months to 1 year post-last 131I treatment. Patients were categorized into two groups based on TgDT<3 years (n=16) and ≥3 years (n=45). The initial and final values of T cell subsets, NK cell percentages, and lymphocyte counts were defined at the first and last Tg measurement points, respectively. The lymphocyte subset change rate was calculated as [ (final value - initial value) /initial value] ×100%. Differences in initial values and change rates of lymphocyte subsets between the two groups were compared. Multivariate Logistic regression analysis was performed to identify factors influencing biochemical progression in DM-PTC. Results The ≥3 years group had a lower age at diagnosis, fewer local surgeries before the last 131I treatment, lower RAIR, TERT mutation, and co-occurrence of BRAF and TERT mutations, but a higher RET fusion rate compared to the <3 years group (P<0.05). The ≥3 years group exhibited higher percentages of CD3+ and CD8+ T cells and lower percentages of NK cells and CD4/CD8 ratio compared to the <3 years group (P<0.05). Multivariate Logistic regression analysis indicated that a decrease in CD8+ T cell percentage (OR=0.879, 95%CI=0.792-0.975) and co-occurrence of BRAF and TERT mutations (OR=7.044, 95%CI=1.368-36.265) were factors influencing biochemical progression in DM-PTC (P<0.05) . Conclusion An immune status characterized by a low proportion of CD8+ T cells and the co-occurrence of BRAF and TERT mutations are influential factors in the biochemical progression of DM-PTC. Lymphocyte subset analysis and combined genetic testing are crucial for disease monitoring and prognosis evaluation in DM-PTC.