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DTC: Long-Term Management and Advanced Cancer Management 32 Table 9. Factors to Review When Considering Kinase Inhibitor Therapy Factors Favoring Kinase Inhibitor Therapy Factors Discouraging Kinase Inhibitor Therapy Imminently threatening disease progression expected to require intervention and/ or to produce morbidity or mortality in <6 months (e.g. pulmonary lesions or lymphadenopathy likely to rapidly invade airways, produce dyspnea, or cause bronchial obstruction). Clinically significant anatomical disease progression in ≤6 months despite optimal TSH suppression in RAI-refractory disease not amenable to control using focal therapeutic approaches (e.g. surgery, radiation therapy, ablation) Comorbidity including: • Active or recent intestinal disease (e.g., diverticulitis, inflammatory bowel disease, recent bowel resection) • Liver disease • Recent bleeding (e.g., ulcer/GI bleed) or coagulopathy • Recent cardiovascular event(s) (e.g., CVA, MI) • Recent tracheal radiation therapy (this is associated with increased risks of aerodigestive fistula with kinase inhibitor therapy) • Cachexia/low weight/poor nutrition • Poorly controlled hypertension • Prolonged QTc interval/history of significant arrhythmia (includes ventricular and bradyarrhythmias) • Untreated brain metastases (controversial) • Recent suicidal ideation (suicide has been reported in depressed patient receiving TKIs) Symptomatic disease (e.g. exertional dyspnea, painful unresectable adenopathy), not adequately addressable using directed therapy. Diffuse disease progression as opposed to focal progression (e.g. in multiple lung metastases, as opposed to a few growing lesions) NOTE: Bone metastases are oen poorly responsive to kinase inhibitor therapy. Life expectancy based upon other co- morbidity estimated to be too brief to justify systemic therapy

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