tbuckley/cabot-search huggingface dataset:
Randomization in Clinical Trials
Authors: Kristine Broglio
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mexican Carriers of the <i>HNF1A</i> p.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas
Authors: Alexandro J. Martagón, Omar Yaxmehen Bello-Chavolla, Olimpia Arellano-Campos, Paloma Almeda-Valdés, Geoffrey A. Walford, Ivette Cruz-Bautista, Donají V. Gómez-Velasco, Roopa Mehta, Liliana Muñoz-Hernández, Magdalena Sevilla-González, Tannia L. Viveros-Ruiz, María Luisa Ordoñez-Sánchez, Rosario Rodríguez-Guillen, Jose C. Florez, María Teresa Tusié-Luna, Carlos A. Aguilar-Salinas, Josep M. Mercader, Alicia Huerta-Chagoya, Hortensia Moreno-Macías, Humberto García-Ortiz, Alisa Manning, Lizz Caulkins, Jason Flannick, Nick Patterson, Angélica Martínez-Hernández, Federico Centeno-Cruz, Francisco Martin Barajas-Olmos, Carlos Zerrweck, Cecilia Contreras-Cubas, Elvia Mendoza-Caamal, Cristina Revilla-Monsalve, Sergio Islas Andrade, Emilio Córdova, Xavier Soberón, María Elena González-Villalpando, Lynne Wilkens, Loic Le Marchand, Kristine Monroe, Laurence Kolonel, Olimpia Arellano-Campos, María L. Ordóñez-Sánchez, Maribel Rodríguez-Torres, Yayoi Segura-Kato, Rosario Rodríguez-Guillén, Ivette Cruz-Bautista, Linda Liliana Muñoz-Hernández, Alexandro J. Martagón, Magdalena del Rocio Sevilla Gonzalez, Donají Gómez, Paloma Almeda-Valdés, Maria Eugenia Garay, Juan Manuel Malacara Hernandez, Noël P. Burtt, Maria L. Cortes, David M. Altshuler, Christopher A. Haiman, Carlos A. Aguilar-Salinas, Clicerio González-Villalpando, Lorena Orozco, Teresa Tusié-Luna, Jose C. Florez
Journal: Diabetes Care (2018)

OBJECTIVE To assess whether an ethnic-specific variant (p.E508K) in the maturity-onset diabetes of the young (MODY) gene hepatocyte nuclear factor-1α (HNF1A) found in Mexicans is associated with higher sensitivity to sulfonylureas, as documented in patients with MODY3. RESEARCH DESIGN AND METHODS We recruited 96 participants (46 variant carriers and 50 age- and sex-matched noncarriers). Response to glipizide (one 2.5–5.0-mg dose), metformin (four 500-mg doses), and an oral glucose challenge was evaluated using a previously validated protocol. Glucose and insulin levels and their areas under the curve (AUCs) were compared between groups. RESULTS Carriers of the p.E508K variant had a lower maximum insulin peak during the glipizide challenge as compared with noncarriers with diabetes (P &amp;lt; 0.05). Also, carriers had a lower insulin response after the oral glucose challenge. Following an oral glucose tolerance test in the presence of metformin, carriers of the p.E508K variant with diabetes had a lower maximum insulin peak and total and incremental insulin AUC value as compared with noncarriers with diabetes (P &amp;lt; 0.05). A similar but nonsignificant trend was seen in participants without type 2 diabetes. CONCLUSIONS Carriers of variant p.E508K in HNF1A have a reduced insulin response rather than the increased sensitivity to sulfonylureas seen in patients with MODY3.
Clinical and biomarker results from phase I/II study of PI3K inhibitor BYL 719 (alpelisib) plus nab-paclitaxel in HER2-negative metastatic breast cancer.
Authors: Priyanka Sharma, Vandana Gupta Abramson, Anne O'Dea, Harsh B Pathak, Ziyan Y. Pessetto, Yen Y. Wang, Karissa Finke, Marc Steven Hoffmann, Manana Elia, Sharon Lewis, Jecinta Scott, Jilliann De Jong, Julia Urban, Jaimie Heldstab, Stephanie LaFaver, Stephen K. Williamson, Greg Reed, Bruce F. Kimler, Qamar J. Khan, Andrew K. Godwin
Journal: Journal of Clinical Oncology (2018)

1018 Background: Activation of Phosphatidylinositol-3-kinase (PI3K) pathway may confer resistance to taxanes and in preclinical models concomitant inhibition of the PI3K pathway enhances efficacy of taxanes. Alpelisib is a potent oral, class I inhibitor of PI3K alpha isoforms with antitumor activity in tumors that harbor PI3KCA mutations. Methods: Eligible patients had HER-2 negative MBC with any number of prior chemotherapy. Phase I was 3+3 dose-escalation design with three dose levels of alpelisib (250mg, 300mg, 350mg) PO daily (D1-28) and nab-Paclitaxel (nP) 100 mg/m2 D 1, 8, 15 every 28 days. Phase II was designed according to Simon's Minimax design. Aims were to determine 1) Recommended Phase II Dose (RPTD), 2) Objective Response Rate (ORR), 3) Progression-free survival (PFS). PIK3CA activating mutations in tumor and circulating tumor DNA (ctDNA) were assessed using next-generation sequencing. Results: There were no DLTs in the three dose levels of phase I (n = 10). 33 patients were treated in phase II on the RPTD (Alpelisib 350mg PO daily plus nP 100mg/m2 D1,8,15 every 28 days). Median age was 55 years; 30% had TNBC. 84% had visceral disease, 74% had received prior chemotherapy for MBC, 84% had received prior taxane. Hyperglycemia (G3:29%,G4:0%), neutropenia (G3:24%,G4:7%), anemia (G3:12%, G4:0%), diarrhea (G3:7%, G4:0%) were the most common grade 3/4 adverse events. In 42 patients evaluable for response, ORR was 57% (24/42) (CR = 2, PR = 22) and an additional 21% demonstrated SD ≥16wks. ORR for patients treated at RPTD was 55% (18/33). Median PFS is 9 months (95% CI: 6-12). Mean duration of treatment is 8 months(2-26 months). 40%(17/42) demonstrated tissue and/or ctDNA PIK3CA mutation (ctDNA/tissue concordance = 70%). Compared to patients without PIK3CA mutation, those with PIK3CA mutation demonstrated significantly better PFS (7 vs 13 months HR = 0.39, p = 0.03). Conclusions: Alpelisib and nP combination shows encouraging efficacy with manageable toxicity in HER2 negative MBC. Efficacy was especially robust in patients with PIK3CA mutation (ORR = 65%, PFS = 13months). Randomized trial of this combination in PIK3CA mutation selected patients is warranted. Clinical trial information: NCT02379247.
Hematologic adverse events following palbociclib (PAL) dose reduction in patients (pts) with hormone receptor‒positive (HR+)/human epidermal growth factor receptor 2‒negative (HER2‒) advanced breast cancer (ABC): Pooled analysis from randomized phase 2 and 3 studies.
Authors: Sunil Verma, Seock-Ah Im, Jungsil Ro, Igor Bondarenko, Norikazu Masuda, Marco Colleoni, Shailendra Verma, Patrick Schnell, Eustratios Bananis, Dongrui (Ray) Lu, Johannes Ettl, Massimo Cristofanilli, Hope S. Rugo, Richard S. Finn
Journal: Journal of Clinical Oncology (2018)

1060 Background: A previous pooled analysis showed that 36.9% of pts receiving PAL required dose reduction, most occurring during the first 6 mo of treatment and with decreasing frequency during subsequent 28-d treatment cycles (C). Previous data have also shown that PAL dose reductions do not affect efficacy (Im S-A, et al. ESMO Asia 2017). Methods: This analysis evaluated the frequency of hematologic adverse events (AEs) 30 d before and after dose reduction (during each treatment C1‒C6) among pts who required PAL dose reduction. Data were pooled from 3 randomized studies: PALOMA-1, a phase 2, open-label study of postmenopausal pts untreated for ABC receiving PAL+letrozole (L) or L alone; PALOMA-2, a phase 3, double-blind study of postmenopausal pts untreated for ABC receiving PAL+L or placebo (PBO)+L; PALOMA-3, a phase 3, double-blind study of pre- or postmenopausal pts who progressed on prior endocrine therapy receiving PAL+fulvestrant (F) or PBO+F. Results: A total of 311 pts with HR+/HER2‒ ABC required a PAL dose reduction (93.6% due to AEs) from 125 to 100 mg. Mean age was 59.9 y, and 46.9% of pts had visceral disease. Median time to dose reduction was 70 d. Incidences of grades 3/4 hematologic AEs were lower after dose reduction (Table), with decreased severity after dose reduction. Conclusions: A decrease in frequency and severity of hematologic AEs, including febrile neutropenia, following PAL dose reduction was observed, supporting the use of dose reduction in AE management. Funding: Pfizer (NCT00721409, NCT01740427, NCT01942135). Clinical trial information: NCT00721409, NCT01740427, NCT01942135.Incidence of AEs (Grades 3/4), % Before Dose Reduction (N = 311) After Dose Reduction C1 (N = 310) C2 (N = 284) C3 (N = 267) C4 (N = 253) C5 (N = 241) C6 (N = 228) Neutropenia 66.2/17.4 35.5/2.9 41.2/3.2 34.8/3.4 36.0/2.4 30.3/2.9 36.8/0.9 Leukopenia 27.7/0.6 8.1/0 7.7/0 8.2/0 6.7/0 5.0/0 6.6/0 Thrombocytopenia 1.6/0.3 1.0/0 1.1/0 0.7/0 0.8/0 0/0 0.4/0 Febrile neutropenia 1.9/0.3 0/0 0/0 0/0 0/0 0.4/0 0/0 Anemia 2.6/0 1.6/0 1.1/0 0.7/0 0.8/0 0.8/0 0.4/0 Funding: Pfizer (NCT00721409, NCT01740427, NCT01942135)
Oxygen-boosted immunogenic photodynamic therapy with gold nanocages@manganese dioxide to inhibit tumor growth and metastases
Authors: Ruijing Liang, Lanlan Liu, Huamei He, Zhikuan Chen, Zhiqun Han, Zhenyu Luo, Zhihao Wu, Mingbin Zheng, Yifan Ma, Lintao Cai
Journal: Biomaterials (2018)
NF-κB–Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis
Authors: Paulo Rodrigues, Saroor A. Patel, Louise Harewood, Ioana Olan, Erika Vojtasova, Saiful E. Syafruddin, M. Nazhif Zaini, Emma K. Richardson, Johanna Burge, Anne Y. Warren, Grant D. Stewart, Kourosh Saeb-Parsy, Shamith A. Samarajiwa, Sakari Vanharanta
Journal: Cancer Discovery (2018)

Abstract Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis–associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB–driven lymphoid element, as a mediator of metastasis in vivo. We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states. Significance: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 850–65. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 781
Phase II (INSPIRE) trial of pembrolizumab (pembro) with serial immune and genomic profiling in patients (pts) with metastatic triple negative breast cancer (mTNBC).
Authors: Zachary William Neil Veitch, David W. Cescon, Sawako Elston, Scott Lien, Cindy Yang, Ben X Wang, Hal K. Berman, Marcus O. Butler, Eitan Amir, Christine Elser, Sevan Hakgor, Amanda Giesler, Trevor John Pugh, Pamela S Ohashi, Lillian L. Siu, Philippe L. Bedard
Journal: Journal of Clinical Oncology (2018)

1094 Background: Pembro is a PD-1 immune checkpoint inhibitor with a low response rate in pretreated mTNBC. In this biomarker driven, investigator-initiated trial we evaluate changes in immune and genomic landscapes of mTNBC pts treated with pembro monotherapy. Methods: Pts with mTNBC, ECOG 0-1, progressing after or ineligible for standard therapy were treated with Pembro 200mg IV q3w. Imaging (RECIST v1.1) was performed every 9 weeks. Pre- and on-treatment (week 6-9) tumor biopsies (bx) were assessed by IHC (C223 antibody) for PD-L1 expression; single cell suspensions were pooled for exome/RNA-sequencing and immunophenotyping (IP) by flow cytometry. Serial blood samples were collected for IP, cytokines, and ctDNA. Results: Of 20 mTNBC pts enrolled, median age was 40 years, 35% had ≥3 lines of therapy, 35% had LDH ≥1.5xULN, 60% had visceral metastases (liver 25%, lung 44%) and 30% had PD-L1+ ( > 1%) tumors. Best response was 1 PR, 3 SD, and 16 PD. One pt discontinued Pembro after 3 cycles due to grade 3 pneumonitis and nephritis with 29% target lesion reduction (near PR). No other grade 3/4 AEs were observed. Grade ≤2 AEs were fatigue (30%), nausea (25%), and diarrhea (20%). After median follow-up of 6.5 months (range 1.8-19.8), mPFS was 2.1 months (95% CI 1.5-3.1) and mOS was 7.4 months (95% CI 6.2-10.7). Pre-/post-treatment bx were performed on 20 and 10 pts respectively, but at time of analysis only 8/20 had sufficient tumor cell content for IP, and 5/20 had genomic analysis. The two pts with PR/near-PR showed T-cell stimulation with increasing CD8 4-1BB levels on blood IP from baseline to cycle 2 (1.96 to 7.95 [% of CD3]; 10.1 to 13 [% of CD3]) relative to non-responders (4.06 to 3.13 [% of CD3]). A third patient with 26% reduction in target lesions but confirmed progression of non-target lesions had POLE (G1750E) mutation with germline BRCA2 mutation. Conclusions: Consistent with previous reports, the response rate to Pembro monotherapy in pre-treated mTNBC was low. Increased expression of 4-1BB on peripheral blood CD8 cells was observed in patients with target lesion reduction. Further analyses are ongoing. Clinical trial information: NCT02644369.
Career Preferences and Perceptions of Cardiology Among US Internal Medicine Trainees
Authors: Pamela S. Douglas, Anne K. Rzeszut, C. Noel Bairey Merz, Claire S. Duvernoy, Sandra J. Lewis, Mary Norine Walsh, Linda Gillam
Journal: JAMA Cardiology (2018)

Few data exist on internal medicine trainees' selection of cardiology training, although this is important for meeting future cardiology workforce needs.To discover trainees' professional development preferences and perceptions of cardiology, and their relationship to trainees' career choice.We surveyed trainees to discover their professional development preferences and perceptions of cardiology and the influence of those perceptions and preferences on the trainees' career choices. Participants rated 38 professional development needs and 19 perceptions of cardiology. Data collection took place from February 2009, through January 2010. Data analysis was conducted from May 2017 to December 2017.Multivariable models were used to determine the association of demographics and survey responses with prospective career choice.A total of 4850 trainees were contacted, and 1123 trainees (of whom 625 [55.7%] were men) in 198 residency programs completed surveys (23.1% response; mean [SD] age, 29.4 [3.5] years). Principal component analysis of survey responses resulted in 8-factor and 6-factor models. Professional development preferences in descending order of significance were stable hours, family friendliness, female friendliness, the availability of positive role models, financial benefits, professional challenges, patient focus, and the opportunity to have a stimulating career. The top perceptions of cardiology in descending order of significance were adverse job conditions, interference with family life, and a lack of diversity. Women and future noncardiologists valued work-life balance more highly and had more negative perceptions of cardiology than men or future cardiologists, who emphasized the professional advantages available in cardiology. Professional development factors and cardiology perceptions were strongly associated with a decision to pursue or avoid a career in cardiology in both men and women.Alignment of cardiology culture with trainees' preferences and perceptions may assist efforts to ensure the continued attractiveness of cardiology careers and increase the diversity of the cardiology workforce.
How Better Communication Skills May Lessen the Need for Physician-Assisted Death
Authors: Jennifer Brokaw
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
<i>Notes from the Field:</i> Crimean-Congo Hemorrhagic Fever Outbreak — Central Uganda, August–September 2017
Authors: Susan Kizito, Paul E. Okello, Benon Kwesiga, Luke Nyakarahuka, Stephen Balinandi, Sophia Mulei, Jackson Kyondo, Alex Tumusiime, Julius Lutwama, Alex R. Ario, Joseph Ojwang, Bao-Ping Zhu
Journal: MMWR Morbidity and Mortality Weekly Report (2018)
Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study
Authors: Sunni L Mumford, Rebecca A Garbose, Keewan Kim, Kerri Kissell, Daniel L Kuhr, Ukpebo R Omosigho, Neil J Perkins, Noya Galai, Robert M Silver, Lindsey A Sjaarda, Torie C Plowden, Enrique F Schisterman
Journal: The Lancet Diabetes & Endocrinology (2018)
Ribociclib (RIB) + fulvestrant (FUL) in postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC): Results from MONALEESA-3.
Authors: Dennis J. Slamon, Patrick Neven, Stephen K. L. Chia, Seock-Ah Im, Peter A. Fasching, Michelino DeLaurentiis, Katarina Petrakova, Giulia Valeria Bianchi, Francisco J. Esteva, Miguel Martin, Xavier Pivot, Gena Vidam, Yingbo Wang, Cristina Karen Rodriguez Lorenc, Michelle Kristine Miller, Tanya Taran, Guy Heinrich Maria Jerusalem
Journal: Journal of Clinical Oncology (2018)

1000 Background: First-line RIB + letrozole significantly prolonged progression-free survival (PFS) in postmenopausal women with HR+, HER2– ABC. Here we report results from MONALEESA-3 (NCT02422615), a Phase 3 randomized, double-blind, placebo-controlled study of RIB + FUL in pts with HR+, HER2− ABC who received no or up to 1 line of prior endocrine therapy (ET) for ABC. Methods: Postmenopausal women with HR+, HER2– ABC were randomized 2:1 (stratified by presence of liver and/or lung metastases and prior ET) to RIB (600 mg/day; 3-weeks-on/1-week-off) + FUL (500 mg) or placebo (PBO) + FUL. Primary objective: investigator-assessed PFS. Secondary objectives included overall survival, overall response rate (ORR), clinical benefit rate (CBR), and safety. Results: 726 pts were enrolled. Baseline pt characteristics were balanced between arms. Median duration from randomization to data cut-off: 20.4 months. The primary objective was met: PFS was significantly improved in the RIB arm vs the PBO arm (hazard ratio: 0.593; 95% confidence interval [CI]: 0.480–0.732; p = 4.10×10–7); median PFS: 20.5 months; 95% CI: 18.5–23.5 vs 12.8 months; 95% CI: 10.9–16.3. Blinded independent review committee data supported primary efficacy results. Consistent PFS benefit was observed in pts with no (hazard ratio: 0.577; 95% CI: 0.415–0.802) and up to 1 line of prior ET for ABC (hazard ratio: 0.565; 95% CI: 0.428–0.744). In pts with measurable disease at baseline, ORR was 41% vs 29% (RIB vs PBO arm; p = 0.003); CBR was 69% vs 60% (p = 0.015). Common all-grade (G) adverse events (AEs; ≥30% of pts; RIB vs PBO arm) were neutropenia (70% vs 2%), nausea (45% vs 28%), and fatigue (31% vs 33%). In the RIB vs PBO arms, G3/4 neutropenia occurred in 47%/7% vs 0%/0% of pts, G3/4 increased ALT in 7%/2% vs < 1%/0%, and G3/4 increased AST in 5%/1% vs 1%/0%. Post-baseline QTcF > 480 ms (RIB vs PBO arm) occurred in 6% vs 3% of pts. Conclusions: RIB + FUL vs PBO + FUL significantly prolonged PFS and demonstrated a manageable safety profile in postmenopausal pts with HR+, HER2– ABC who received no or up to 1 line of prior ET for advanced disease. RIB + FUL may, therefore, be a treatment option for this pt population. Clinical trial information: NCT02422615.
An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors
Authors: Tao Wang, Rong Lu, Payal Kapur, Bijay S. Jaiswal, Raquibul Hannan, Ze Zhang, Ivan Pedrosa, Jason J. Luke, He Zhang, Leonard D. Goldstein, Qurratulain Yousuf, Yi-Feng Gu, Tiffani McKenzie, Allison Joyce, Min S. Kim, Xinlei Wang, Danni Luo, Oreoluwa Onabolu, Christina Stevens, Zhiqun Xie, Mingyi Chen, Alexander Filatenkov, Jose Torrealba, Xin Luo, Wenbin Guo, Jingxuan He, Eric Stawiski, Zora Modrusan, Steffen Durinck, Somasekar Seshagiri, James Brugarolas
Journal: Cancer Discovery (2018)

By leveraging tumorgraft (patient-derived xenograft) RNA-sequencing data, we developed an empirical approach, DisHet, to dissect the tumor microenvironment (eTME). We found that 65% of previously defined immune signature genes are not abundantly expressed in renal cell carcinoma (RCC) and identified 610 novel immune/stromal transcripts. Using eTME, genomics, pathology, and medical record data involving >1,000 patients, we established an inflamed pan-RCC subtype (IS) enriched for regulatory T cells, natural killer cells, T