Immunotherapy of thyroid cancer

Introduction Recent advancements have significantly transformed the landscape of thyroid carcinoma management. A deeper understanding of tumor genomics has enhanced the ability to monitor indolent disease, allowing for more personalized and targeted therapeutic interventions. Insights into critical molecular pathways, particularly the MAP-kinase and PI۳-kinase pathways, have provided clinicians with new tools to predict the behavior of thyroid cancers and to devise appropriate treatment strategies. This evolution has prompted a reevaluation of treatment approaches, particularly in the context of advanced disease. Methods Current research is increasingly focused on the interactions between tumors, their microenvironments, and the host immune system. Specifically, studies are investigating how factors derived from the bone marrow microenvironment influence tumor growth and progression. Additionally, the role of immunotherapy in thyroid cancer treatment is gaining attention, with a particular emphasis on immune checkpoint inhibitors that have shown promise in various cancers. In the study conducted by Capdevila and colleagues, ۴۲ patients with predominantly metastatic anaplastic thyroid cancer (ATC) were enrolled in the phase II portion of a phase I/II trial. Patients were treated with spartalizumab (PDR۰۰۱), a PD-۱ inhibitor, administered intravenously at a dose of ۴۰۰ mg every ۴ weeks. The majority of patients had been pre-treated with surgery (۶۷%), radiotherapy (۷۱%), and at least one line of systemic therapy (۶۰%), including chemotherapy and targeted therapy. The overall response rate (ORR) was assessed using RECIST v۱.۱ and was found to be ۱۹%, with ۳ complete responses and ۵ partial responses. An additional ۲ patients achieved partial responses based on immune-related response criteria. Responses were observed in both BRAF V۶۰۰E mutant and wild-type tumors. Most responses were observed in patients with PD-L۱-positive tumors, defined as PD-L۱ expression in ≥۱% of tumor cells. Ongoing studies are investigating the potential of combination therapies targeting both the PD-۱/PD-L۱ axis and molecular pathways, along with correlative studies to identify predictive biomarkers. Results In this study, the use of spartalizumab in patients with advanced anaplastic thyroid cancer (ATC) demonstrated an overall response rate of ۱۹%, with ۳ complete responses and ۵ partial responses. Patients with PD-L۱-positive tumors had a response rate of ۲۹%, while those with PD-L۱-negative tumors showed no responses, with a median overall survival of ۱.۶ months. The duration of response ranged from ۱۶.۷ weeks to ۱.۶ years, and ۱۱ patients received treatment for more than ۵۰ weeks. However, resistance to treatment in certain types of thyroid cancer remains challenging, indicating the need for further research. Conclusions Recent advancements in understanding thyroid carcinoma and key molecular pathways have facilitated personalized treatment approaches. The study by Capdevila et al. highlights the potential of spartalizumab in advanced anaplastic thyroid cancer (ATC), achieving a ۱۹% overall response rate, particularly in PD-L۱-positive patients. However, challenges like treatment resistance underscore the need for ongoing clinical trials to address knowledge gaps in immunotherapy. Future research should focus on optimizing patient selection and overcoming resistance mechanisms. With these advancements, immunotherapy has the potential to become a primary treatment option, offering new hope for patients with limited alternatives.

کلیدواژه ها:

thyroid cancer ، immunotherapy ، targeted therapy