Real-World Outcomes and Prognostic Factors in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Sorafenib: A Multicenter Study
Suheda Atas Ipek, Sendag Yaslikaya, Ismail Oguz Kara, Tolga Koseci, Ertugrul Bayram, Esra Asarkaya, Hatice Asoglu, Mehmet Turker, Abdurrahman Aykut, Seda Jeral Evinc, Ozkan Alan, Mehmet Emin Yilmaz, Ozturk Ates, Hatime Arzu Yasar, Mehmet Kayaalp, Esra Asik, Atila Yildirim, Burcu Bacak, Meltem Baykara, Dicle Yurdatap Koc, Muhammed Bekir Hacioglu, Suleyman Alkan, Ferhat Ekinci, Ahmet Burak Agaoglu, Mesut Yilmaz, Ilhan Hacibekiroglu, Mustafa Karaca, Taliha Guclu Kantar, Gamze Gokoz Dogu, Tuba Karacelik, Melek Karakurt Eryilmaz, Teoman Sakalar, Sedat Biter, Mehmet Mutlu Kıdı, Yasemin Aydınalp Camadan, Mahmut BuyuksimsekBackground: Sorafenib remains an important treatment option for patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). This study evaluated real-world outcomes and prognostic factors in patients treated with sorafenib. Materials and Methods: This retrospective multicenter study included 176 patients with RAI-R DTC treated with sorafenib between 2000 and 2024 across sixteen centers. Clinical, pathological and treatment-related variables, including metastatic sites, radiotherapy, dose reduction, inflammatory markers (neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) and pretreatment thyroglobulin (Tg), were analyzed. Progression-free survival (PFS) was evaluated using Kaplan–Meier analysis. Prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results: The median follow-up duration was 24 months and the median PFS was 21 months (95% CI: 15.5–26.5). Partial response was observed in 82 patients (46.6%), stable disease in 55 (31.3%) and progressive disease in 35 (19.9%). Patients who underwent dose reduction had longer PFS than those without dose reduction (42 vs. 19 months, p = 0.030), and absence of dose reduction remained independently associated with progression risk. Patients who received radiotherapy had shorter PFS than those who did not receive radiotherapy (16 vs. 37 months, p = 0.002), and radiotherapy-related variables remained independent predictors of progression. Patients with PLR values >138.2 had shorter PFS than those with PLR values ≤ 138.2 (19 vs. 34 months, p = 0.047), although this association was not maintained in Cox regression analysis. Similarly, associations between NLR and Tg values and PFS did not reach statistical significance (p = 0.112 and p = 0.072, respectively). Hand–foot syndrome was the most common toxicity, occurring in 59 patients (33.5%), while Grade 3 hand–foot syndrome was observed in 7 patients (4.0%). Conclusions: Sorafenib provided meaningful disease control with a median PFS of 21 months in this real-world cohort. Dose reduction was associated with longer PFS, whereas radiotherapy requirement appeared to reflect a higher-risk subgroup. Toxicities were generally manageable.