How can I validate a nomogram? Show me the model.

therapies approved; capecitabine plus lapatinib is an option [4, 5]. With regard to trastuzumab, its activity in the CNS has always been considered very poor, because of difficulty of penetration and insufficient activation of antibody-dependent cellular cytotoxicity (ADCC) in the brain. We report the case of a 63-year-old woman with HER2-positive brain metastases who experienced long-term remission during treatment with T-DM1. The patient was offered T-DM1 as sixth line of treatment in the setting of a disease progressing at multiple sites in the bone and the brain. Prior treatments included several lines of chemotherapy combined with antiHER2 agents: docetaxel/trastuzumab; cisplatin/trastuzumab; lapatinib/capecitabine; trastuzumab/vinorelbine; cisplatin/gemcitabine. The diagnosis of brain metastases (two bilateral cerebellar lesions with maximum size of 6 mm), was performed in December 2006, for which she received stereotactic radiotherapy followed by a partial brain irradiation 8 months later, because of the appearance of two new centimetric lesions in the frontal region. After that, owing to the administration of several lines of treatments, the brain lesions were substantially controlled until February 2013, when it was documented brain progression disease (a new left frontal lesion of 18 mm and a new cerebellar lesion of 22 mm) while bone lesions were stable. The patient had no neurological symptoms with KPS 100%. Therefore, in March 2013, the patient was treated systemically with T-DM1 (3.6 mg/kg/3 weeks). The treatment was well tolerated and a progressive significant decrease in size of the brain lesions was observed (the frontal metastases reduced from 18 to 3 mm and the cerebellar lesion from 22 to 4 mm). No new brain lesions were evident and neither neurological symptoms nor a deterioration of her general health status was observed for 15 months of T-DM1 therapy, until meningeal carcinomatosis occurred. According to Krop’s experience, our case shows that T-DM1 could play a significant role in the treatment of brain metastases even in patients with heavily pretreated HER2-positive metastatic breast cancer. These patients currently have limited treatment options and poor prognosis, with median survival from diagnosis of CNS metastases of 13 months [3]. Our patient, combining systemic and local therapies, lived 92 months from the diagnosis of CNS disease. Possible explanations for the effectiveness of the treatment could be the impaired blood–brain barrier enabling the penetration of T-DM1 into the CNS compartment, the ability of emtansine to activate the ADCC in the brain and the improved control of systemic extracranial disease. This case suggests that T-DM1 is worthy of further investigation in patients with HER2-positive brain metastases.