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Patients with radioactive iodine (RAI) refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis. This article reviews the definition of RAI-refractory thyroid cancer and the management approach. Watchful waiting should be considered for patients with asymptomatic and non-progressive disease, while oral targeted agent with tyrosine kinase inhibitors can be considered for patients who are symptomatic or whose disease would cause irreversible complications if treatment has not been initiated. Since these targeted agents only improve disease-free survival and are associated with adverse events, physicians should assess both clinical and tumor factors carefully to decide on the right timing of start of palliative treatment., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Most patients with well-differentiated thyroid cancers (WDTC) are adequately treated with surgery, radioactive iodine, and TSH suppression by thyroxine. External radiotherapy (ERT) is reserved for selected cases and for older patients. Some of the indications for ERT to neck include adjuvant treatment for gross or microscopic disease after surgery, palliation of locally advanced unresectable tumor, or as salvage for recurrent disease which is not amenable to surgery or does not uptake radioactive iodine. High radiation dose of at least 60Gy is required for locoregional control of gross or microscopic residual disease. As even patients with recurrent or metastatic disease can have long survival, it is important to minimize late radiation-induced morbidity without compromising local control. Modern ERT technique like intensity-modulated radiotherapy allows high radiation dose to be delivered to the large, complex target volume while protecting the adjacent critical normal structures like the trachea, larynx, esophagus, and cervical spinal cord., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Radioactive iodine is given after total thyroidectomy for remnant ablation or treatment of residual/metastatic disease. The decision and dose of radioactive iodine should be in a personalized and patient-specific approach, taking account the clinical-pathological features, risk stratification, patient's preference, and facilities of the institutions. We review the principles and use of radioactive iodine in differentiated thyroid cancer., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Cervical esophageal carcinoma (CEC) is rare, accounting for 2-10% of esophageal cancers and is mostly squamous cell carcinoma. Because of the anatomical proximity of CEC to larynx, surgical treatment would involve pharyngo-laryngo-esophagectomy (PLE) with inherent high mortality and morbidity. Laryngeal preservation is an important consideration, and definitive chemoradiotherapy is the recommended treatment. Treatment strategy of CEC can be more akin to treatment for head and neck cancers than to thoracic esophageal cancers. Since the exact location, extent of primary and nodal metastasis varies between patients, radiotherapy treatment needs to be individualized. The optimal radiation dose for CEC is uncertain, but retrospective data suggests that higher radiation dose of at least 60 Gy is associated with better local control and survival. Advanced radiotherapy technique, like intensity modulated radiotherapy, is usually required to achieve high dose to tumor while protecting normal tissues from excessive radiation.

With more understanding of the tumor biology, esophageal squamous cell carcinoma (ESCC) and adenocarcinoma are increasingly recognized as different disease entities and are managed with different treatment approaches. Most patients with ESCC need systemic treatment at some point of their disease course, but only until recently, the progress in systemic treatment has been relatively stagnant compared with its adenocarcinoma counterpart. Platinum-based regimens remain the standard of care, while taxanes have been increasingly used upfront and in later lines of treatment. The attempts to personalize treatment for ESCC with various target therapies have been futile. Immune checkpoint inhibitors are now coming into play with promising activity and potentials to combine with different treatment modalities. The current chapter overviews the systemic treatment for ESCC and highlights the recent development.

Esophageal squamous cell carcinoma (ESCC) is an aggressive disease. Many patients have locally advanced disease or already have distant metastasis at presentation. Radiotherapy plays an important role in the treatment of esophageal squamous cell carcinoma. Neoadjuvant chemoradiotherapy improves the survival and surgical outcome compared to surgery alone. Definitive radiotherapy (RT) with or without chemotherapy is used in patients who decline surgery or are medically inoperable. Palliative radiotherapy using external beam radiotherapy or intraluminal brachytherapy is effective for dysphagia and pain control.d.