*2.5.3 Secondary malignant neoplasms*

As patients with heritable RB age, the risk of non-ocular malignancies significantly increases. These tumors include osteosarcoma, soft tissue sarcoma, epithelial cancers, and melanoma. It has been suggested that a greater risk for second cancers occurs in patients with familial RB compared with those with a de novo RB1 mutation [72]. External beam radiation therapy for patients with heritable disease has a further increased risk of developing second malignancies.
