• The observation that a patient does not demonstrate radioiodine uptake on a diagnostic scan or posttherapy scan does not necessarily mean that the patient’s metastatic disease is radioiodine refractory.

• The observation that a patient does demonstrate radioiodine uptake on a diagnostic scan or posttherapy scan does not necessarily mean that the patient’s metastatic disease is responsive to a ¹³¹I therapy.

• As the total accumulative activity of administered ¹³¹I increases, the likelihood of a response to a subsequent ¹³¹I therapy decreases. However, no maximum accumulated threshold of administered ¹³¹I activity should designate a patient’s metastatic disease as radioiodine refractory.

• One metastatic lesion that is classified as radioiodine refractory does not necessarily mean the patient is now radioiodine refractory. Combination therapy of direct focal therapy (e.g., surgery, external-beam radiotherapy, radiofrequency ablation, cryotherapy, embolization, radioisotope embolization) or/with targeted therapy (e.g., tyrosine kinase inhibitors, BRAF inhibitors, etc.) in combination with ¹³¹I therapy may benefit the patient.

• Progression, in and of itself, is not a criterion that a ¹³¹I therapy has “failed” and that a patient’s metastatic disease is “radioiodine refractory.” Additional factors, such as duration of progression-free survival and administered activity of ¹³¹I are important.