Renal cell carcinoma with brain metastases is known as to have a poor prognosis. region with perilesional edema in magnetic resonance imaging (MRI) of brain and an enhancing renal lower polar mass measuring about 10?cm??6?cm on computerised tomography (CT) of abdomen with subcentimetric parenchymal nodules in basal lung filed largest measuring 7?mm. Renal biopsy confirmed the primary to be clear cell carcinoma (ISUP grade 2). As per the recommendation by the multidisciplinary tumour board, the patient was treated with radiation therapy (single-fraction frameless stereotactic radiosurgery to the brain lesion 13?Gy) for brain lesion followed by sunitinib therapy at an oral dose of 50?mg daily for 4?weeks on and 2?weeks off. Dexamethasone 16?mg was also given daily, which was progressively decreased until discontinuation during the following months. MRI of the brain (March 2014) revealed complete remission of the tumour (Figure 1). Computerised tomography of abdomen (April 2014) revealed a reduction in the size of renal mass (Figure 2). The patient underwent laparoscopic radical nephrectomy in April 2014. By February 2017, there was complete remission of brain and Thiamine pyrophosphate chest metastasis, but was found to have a lesion in the right kidney, for which the patient underwent radiofrequency ablation in March 2017. The procedure was uneventful and the patient was put on regular follow-up. Open in a separate window Figure 1. (A) MRI lesion in brain and (B) MRI lesion responding completely to TKI. MRI indicates magnetic resonance imaging; TKI, tyrosine kinase inhibitor. Open in a separate window Figure 2. (A) Kidney tumour before staring TKI and (B) primary tumour after TKI. TKI indicates tyrosine kinase inhibitor. The patient developed chronic renal failure with serum creatinine level reaching 6.8?mg/dL and proteinuria. As a result, sunitinib was reduced to 25?mg OD (duration of therapy 40?months) and later changed to sorafenib 200?mg BD (on sorafenib LGR3 for 21?months till last follow-up). There was Thiamine pyrophosphate no worsening of serum creatinine level with sorafenib therapy; therefore, sorafenib 200?mg was continued. The individual does well till last follow-up in November 2018 (5?years from preliminary diagnosis). Dialogue The prognosis of mind metastases in RCC offers typically been dismal.2 Cytokines used in RCC have limited central nervous system (CNS) efficacy4 as it does not cross the blood-brain barrier. Tyrosine kinase inhibitor showed better response in metastatic RCC1 and is considered to be the standard of care now. The efficacy of sorafenib, sunitinib, and temsirolimus in CNS is not known because the previous phase 3 trial with these drugs have excluded patients with CNS disease.5C7 Management of brain metastasis in the renal tumour is still controversial even though there are case Thiamine pyrophosphate reports about the benefit of TKI in this scenario. A case reported in Greece on March 2007 showed the activity of sunitinib in brain metastases from RCC, in which the patient had a partial response of the cerebral lesion following treatment with sunitinib. Sunitinib was safe and led to a considerable shrinkage of the brain metastases without any serious adverse reactions or CNS toxicities.8 The role of cytoreductive nephrectomy is disputed in these patients due to limited survival. In our case, the brain metastases in RCC showed excellent response to sunitinib therapy and radiotherapy, leading to complete remission of the lesion in the brain, and hence a cytoreductive nephrectomy was advised Thiamine pyrophosphate later. This case shows that we can have an excellent response in select patients with a low burden of metastasis in the brain. Probably, the initial radiotherapy could have helped the penetration of the small TKI molecules across the blood-brain barrier leading to the excellent response to the treatment.9 Conclusions Even though RCC with brain metastases is considered to have a poor prognosis, they can have an excellent response with a combination of radiation and TKI. If there is a good response, they may be considered for cytoreductive nephrectomy. Further studies in this area may help in identifying factor predicting response to radiation and TKI in such patients. Footnotes Funding:The author(s) received no financial support for the research, authorship, and/or publication of the content. Declaration of conflicting passions:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Contributed by Author Contributions: All authors contributed equally in the write-up and editing of the article. ORCID identification: Abhishek Laddha https://orcid.org/0000-0003-1761-1783.