Citations 2
An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma
Hasanov, Elshad , Yeboa, D.N. , Tucker, Mathew D., Swanson, Todd A. , Ene, Chibawanye , Hasanov, Merve , Derks, Sophie H. A. E. , Smits, Marion , Dudani, Shaan , Heng, Daniel Y.C., Bex, Axel , Hanalıoğlu, Şahin , Weinberg, Jeffrey S. , Hirsch, Laure , Carlo, Maria I. , Aizer, Ayal A. , Brown, Paul D. , Bilen, Mehmet Asım , Chang, Eric L. , Jaboin, Jerry J. , Choueiri, Toni K. , Halasz, Lia M. , Patel, Toral , Soltys, Scott G. , Elder, J. Bradley , Başkaya, Mustafa K. , Timmerman, Robert , Kim, Michelle Miran, Mut, Melike , Beal, Kathryn , Lang, Frederick F. , Giles, Rachel , Patel, Toral , Brown, Paul David, Choueiri, Toni K , Smits, Marion , Hanalioglu, Sahin , Patel, Toral R , Beckham, Thomas Hendrix , Rini, Brian I. , Brastianos, Priscilla K. , Brugarolas, James , Atkins, Michael B. , McGregor, Bradley A. , McDermott, David F. , Yu, James B. , Kim, Michelle H. , Markert, James M. , Tannir, Nizar , Samandouras, George , Jonasch, Eric W.
CA: A Cancer Journal for Clinicians | June 16, 2022 | Volume: 72 | Issue: 5 | Pages: 454-489
Abstract Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454‐489.
Mutations in TSC1, TSC2, and MTOR Are Associated with Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma
Choueiri, Toni K. , Fay, André P. , Velasco, Guillermo de , Tyburczy, Magdalena E. , Hamieh, Lana , Albigès, Laurence , Ho, Thai H. , Song, Jiaxi , Pignon, Jean‐Christophe , Barrios, Pablo M. , Michaelson, M. Dror , Krajewski, Katherine M. , Porta, Camillo , Pal, Sumanta K. , Heng, Daniel Y.C., Gray, Kathryn P. , Kwiatkowski, David J. , Rini, Brian I. , Thorner, Aaron R. , Agarwal, Neeraj , Van Allen, Eliezer M , Bellmunt, Joaquim , McDermott, David F. , Signoretti, Sabina , Ho, Thai , Choueiri, Toni K
Clinical Cancer Research | February 1, 2016 | Volume: 22 | Issue: 10 | Pages: 2445-2452
Abstract Purpose: We examined the hypothesis that mutations in mTOR pathway genes are associated with response to rapalogs in metastatic renal cell carcinoma (mRCC). Experimental Design: We studied a cohort of mRCC patients who were treated with mTOR inhibitors with distinct clinical outcomes. Tumor DNA from 79 subjects was successfully analyzed for mutations using targeted next-generation sequencing of 560 cancer genes. Responders were defined as those with partial response (PR) by RECIST v1.0 or stable disease with any tumor shrinkage for 6 months or longer. Nonresponders were defined as those with disease progression during the first 3 months of therapy. Fisher exact test assessed the association between mutation status in mTOR pathway genes and treatment response. Results: Mutations in MTOR, TSC1, or TSC2 were more common in responders, 12 (28%) of 43, than nonresponders, 4 (11%) of 36 (P = 0.06). Mutations in TSC1 or TSC2 alone were also more common in responders, 9 (21%), than nonresponders, 2(6%), (P = 0.05). Furthermore, 5 (42%) of 12 subjects with PR had mutations in MTOR, TSC1, or TSC2 compared with 4 (11%) of 36 nonresponders (P = 0.03). Eight additional non-mTOR pathway genes were found to be mutated in at least 4 of 79 tumors (5%); none were associated positively with response. Conclusions: In this cohort of mRCC patients, mutations in MTOR, TSC1, or TSC2 were more common in patients who experienced clinical benefit from rapalogs than in those who progressed. However, a substantial fraction of responders (24 of 43, 56%) had no mTOR pathway mutation identified. Clin Cancer Res; 22(10); 2445–52. ©2016 AACR. See related commentary by Voss and Hsieh, p. 2320