493 results on '"Maria J. Merino"'
Search Results
2. Evaluating Diagnostic Accuracy and Inter-reader Agreement of the Prostate Imaging After Focal Ablation Scoring System
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David G. Gelikman, Alexander P. Kenigsberg, Yan Mee Law, Enis C. Yilmaz, Stephanie A. Harmon, Sahil H. Parikh, Jason A. Hyman, Hannah Huth, Christopher R. Koller, Daniel Nethala, Charles Hesswani, Maria J. Merino, Sandeep Gurram, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto, and Baris Turkbey
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Focal therapy ,Magnetic resonance imaging ,Post-treatment surveillance ,Prostate ablation ,Prostatic neoplasms ,Diseases of the genitourinary system. Urology ,RC870-923 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background and objective: Focal therapy (FT) is increasingly recognized as a promising approach for managing localized prostate cancer (PCa), notably reducing treatment-related morbidities. However, post-treatment anatomical changes present significant challenges for surveillance using current imaging techniques. This study aimed to evaluate the inter-reader agreement and efficacy of the Prostate Imaging after Focal Ablation (PI-FAB) scoring system in detecting clinically significant prostate cancer (csPCa) on post-FT multiparametric magnetic resonance imaging (mpMRI). Methods: A retrospective cohort study was conducted involving patients who underwent primary FT for localized csPCa between 2013 and 2023, followed by post-FT mpMRI and a prostate biopsy. Two expert genitourinary radiologists retrospectively evaluated post-FT mpMRI using PI-FAB. The key measures included inter-reader agreement of PI-FAB scores, assessed by quadratic weighted Cohen’s kappa (κ), and the system’s efficacy in predicting in-field recurrence of csPCa, with a PI-FAB score cutoff of 3. Additional diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also evaluated. Key findings and limitations: Scans from 38 patients were analyzed, revealing a moderate level of agreement in PI-FAB scoring (κ = 0.56). Both radiologists achieved sensitivity of 93% in detecting csPCa, although specificity, PPVs, NPVs, and accuracy varied. Conclusions and clinical implications: The PI-FAB scoring system exhibited high sensitivity with moderate inter-reader agreement in detecting in-field recurrence of csPCa. Despite promising results, its low specificity and PPV necessitate further refinement. These findings underscore the need for larger studies to validate the clinical utility of PI-FAB, potentially aiding in standardizing post-treatment surveillance. Patient summary: Focal therapy has emerged as a promising approach for managing localized prostate cancer, but limitations in current imaging techniques present significant challenges for post-treatment surveillance. The Prostate Imaging after Focal Ablation (PI-FAB) scoring system showed high sensitivity for detecting in-field recurrence of clinically significant prostate cancer. However, its low specificity and positive predictive value necessitate further refinement. Larger, more comprehensive studies are needed to fully validate its clinical utility.
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- 2024
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3. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
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Christopher J. Ricketts, Aguirre A. De Cubas, Huihui Fan, Christof C. Smith, Martin Lang, Ed Reznik, Reanne Bowlby, Ewan A. Gibb, Rehan Akbani, Rameen Beroukhim, Donald P. Bottaro, Toni K. Choueiri, Richard A. Gibbs, Andrew K. Godwin, Scott Haake, A. Ari Hakimi, Elizabeth P. Henske, James J. Hsieh, Thai H. Ho, Rupa S. Kanchi, Bhavani Krishnan, David J. Kwiatkowski, Wenbin Liu, Maria J. Merino, Gordon B. Mills, Jerome Myers, Michael L. Nickerson, Victor E. Reuter, Laura S. Schmidt, C. Simon Shelley, Hui Shen, Brian Shuch, Sabina Signoretti, Ramaprasad Srinivasan, Pheroze Tamboli, George Thomas, Benjamin G. Vincent, Cathy D. Vocke, David A. Wheeler, Lixing Yang, William Y. Kim, A. Gordon Robertson, Paul T. Spellman, W. Kimryn Rathmell, and W. Marston Linehan
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Biology (General) ,QH301-705.5 - Published
- 2024
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4. High-throughput and targeted drug screens identify pharmacological candidates against MiT-translocation renal cell carcinoma
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Martin Lang, Laura S. Schmidt, Kelli M. Wilson, Christopher J. Ricketts, Carole Sourbier, Cathy D. Vocke, Darmood Wei, Daniel R. Crooks, Youfeng Yang, Benjamin K. Gibbs, Xiaohu Zhang, Carleen Klumpp-Thomas, Lu Chen, Rajarshi Guha, Marc Ferrer, Crystal McKnight, Zina Itkin, Darawalee Wangsa, Danny Wangsa, Amy James, Simone Difilippantonio, Baktir Karim, Francisco Morís, Thomas Ried, Maria J. Merino, Ramaprasad Srinivasan, Craig J. Thomas, and W. Marston Linehan
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MiT family translocation RCC ,TFE3-RCC ,TFE3-fusion ,GPNMB ,RCC therapy ,NVP-BGT226 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background MiT-Renal Cell Carcinoma (RCC) is characterized by genomic translocations involving microphthalmia-associated transcription factor (MiT) family members TFE3, TFEB, or MITF. MiT-RCC represents a specific subtype of sporadic RCC that is predominantly seen in young patients and can present with heterogeneous histological features making diagnosis challenging. Moreover, the disease biology of this aggressive cancer is poorly understood and there is no accepted standard of care therapy for patients with advanced disease. Tumor-derived cell lines have been established from human TFE3-RCC providing useful models for preclinical studies. Methods TFE3-RCC tumor derived cell lines and their tissues of origin were characterized by IHC and gene expression analyses. An unbiased high-throughput drug screen was performed to identify novel therapeutic agents for treatment of MiT-RCC. Potential therapeutic candidates were validated in in vitro and in vivo preclinical studies. Mechanistic assays were conducted to confirm the on-target effects of drugs. Results The results of a high-throughput small molecule drug screen utilizing three TFE3-RCC tumor-derived cell lines identified five classes of agents with potential pharmacological efficacy, including inhibitors of phosphoinositide-3-kinase (PI3K) and mechanistic target of rapamycin (mTOR), and several additional agents, including the transcription inhibitor Mithramycin A. Upregulation of the cell surface marker GPNMB, a specific MiT transcriptional target, was confirmed in TFE3-RCC and evaluated as a therapeutic target using the GPNMB-targeted antibody-drug conjugate CDX-011. In vitro and in vivo preclinical studies demonstrated efficacy of the PI3K/mTOR inhibitor NVP-BGT226, Mithramycin A, and CDX-011 as potential therapeutic options for treating advanced MiT-RCC as single agents or in combination. Conclusions The results of the high-throughput drug screen and validation studies in TFE3-RCC tumor-derived cell lines have provided in vitro and in vivo preclinical data supporting the efficacy of the PI3K/mTOR inhibitor NVP-BGT226, the transcription inhibitor Mithramycin A, and GPNMB-targeted antibody-drug conjugate CDX-011 as potential therapeutic options for treating advanced MiT-RCC. The findings presented here should provide the basis for designing future clinical trials for patients with MiT-driven RCC.
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- 2023
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5. TFEB and TFE3 drive kidney cystogenesis and tumorigenesis
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Chiara Di Malta, Angela Zampelli, Letizia Granieri, Claudia Vilardo, Rossella De Cegli, Laura Cinque, Edoardo Nusco, Salvatore Pece, Daniela Tosoni, Francesca Sanguedolce, Nicolina Cristina Sorrentino, Maria J Merino, Deborah Nielsen, Ramaprasad Srinivasan, Mark W Ball, Christopher J Ricketts, Cathy D Vocke, Martin Lang, Baktiar Karim, Luisa Lanfrancone, Laura S Schmidt, W Marston Linehan, and Andrea Ballabio
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BHD ,cysts ,kidney cancer ,TFE3 ,TFEB ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Abstract Birt‐Hogg‐Dubé (BHD) syndrome is an inherited familial cancer syndrome characterized by the development of cutaneous lesions, pulmonary cysts, renal tumors and cysts and caused by loss‐of‐function pathogenic variants in the gene encoding the tumor‐suppressor protein folliculin (FLCN). FLCN acts as a negative regulator of TFEB and TFE3 transcription factors, master controllers of lysosomal biogenesis and autophagy, by enabling their phosphorylation by the mechanistic Target Of Rapamycin Complex 1 (mTORC1). We have previously shown that deletion of Tfeb rescued the renal cystic phenotype of kidney‐specific Flcn KO mice. Using Flcn/Tfeb/Tfe3 double and triple KO mice, we now show that both Tfeb and Tfe3 contribute, in a differential and cooperative manner, to kidney cystogenesis. Remarkably, the analysis of BHD patient‐derived tumor samples revealed increased activation of TFEB/TFE3‐mediated transcriptional program and silencing either of the two genes rescued tumorigenesis in human BHD renal tumor cell line‐derived xenografts (CDXs). Our findings demonstrate in disease‐relevant models that both TFEB and TFE3 are key drivers of renal tumorigenesis and suggest novel therapeutic strategies based on the inhibition of these transcription factors.
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- 2023
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6. MRI-guided focal laser ablation of prostate cancer: a prospective single-arm, single-center trial with 3 years of follow-up
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Sherif Mehralivand, Arvin K. George, Anthony N. Hoang, Soroush Rais-Bahrami, Ardeshir R. Rastinehad, Amir H. Lebastchi, Michael Ahdoot, Mohummad Minhaj Siddiqui, Jonathan Bloom, Abhinav Sidana, Maria J. Merino, Peter L. Choyke, Joanna H. Shih, Baris Turkbey, Bradford J. Wood, and Peter A. Pinto
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
PURPOSEWe aimed to assess post-interventional and 36-month follow-up results of a single-center, single-arm, in-bore phase I trial of focal laser ablation (FLA) guided by multiparametric magnetic resonance imaging (mpMRI).METHODSFLA procedures were done in-bore MRI using a transperineal approach. Primary endpoints were feasibility and safety expressed as lack of grade 3 complications. Secondary endpoints were changes in international prostate symptom score (IPSS), sexual health inventory for men (SHIM), quality of life (QoL) scores, and serum prostate specific antigen (PSA) levels. Treatment outcomes were assessed by combined mpMRI-ultrasound fusion-guided and extended sextant systematic biopsy after 12, 24, and optionally after 36 months.RESULTSFifteen participants were included. Seven patients (46.67%) had Gleason 3+3 and 8 patients (53.33%) had Gleason 3+4 cancer. All patients tolerated the procedure well, and no grade 3/4 complications occurred. All grade 1 and 2 complications were transient and resolved completely. There was no significant change in mean IPSS from baseline (-1, p = 0.460) and QoL (0, p = 0.441) scores following FLA but there was a significant drop in mean SHIM scores (-2, p = 0.010) compared to pretreatment baselines. Mean PSA significantly decreased after FLA (-2.5, p < 0.001). Seven out of 15 patients (46.67%) had residual cancer in, adjacent, or in close proximity to the treatment area (1 × 4+3=7, 1 × 3+4=7, and 5 × 3+3=6). Four out of 15 patients (26.67%) underwent salvage therapy (2 repeat FLA, 2 radical prostatectomy).CONCLUSIONAfter 3 years of follow-up we conclude focal laser ablation is safe and feasible without significant complications.
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- 2021
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7. A case report of multiple primary prostate tumors with differential drug sensitivity
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Scott Wilkinson, Stephanie A. Harmon, Nicholas T. Terrigino, Fatima Karzai, Peter A. Pinto, Ravi A. Madan, David J. VanderWeele, Ross Lake, Rayann Atway, John R. Bright, Nicole V. Carrabba, Shana Y. Trostel, Rosina T. Lis, Guinevere Chun, James L. Gulley, Maria J. Merino, Peter L. Choyke, Huihui Ye, William L. Dahut, Baris Turkbey, and Adam G. Sowalsky
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Science - Abstract
Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy.
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- 2020
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8. Adrenocortical carcinoma masquerading as pheochromocytoma: a histopathologic dilemma
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Impana Shetty, Sarah Fuller, Margarita Raygada, Maria J Merino, B J Thomas, Brigitte C Widemann, Karlyne M Reilly, Karel Pacak, and Jaydira Del Rivero
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Adrenocortical carcinoma (ACC) is an aggressive cancer that originates in the cortex of the adrenal gland and generally has a poor prognosis. ACC is rare but can be more commonly seen in those with cancer predisposition syndromes (e.g. Li-Fraumeni and Lynch Syndrome). The diagnosis of ACC is sometimes uncertain and it requires the use of precise molecular pathology; the differential diagnosis includes pheochromocytoma, adrenal adenoma, renal carcinoma, or hepatocellular carcinoma. We describe a case of a 57-year-old woman with Lynch Syndrome and metastatic ACC who was initially diagnosed as having pheochromocytoma. The tumor was first identified at 51 years of age by ultrasound followed by a CT scan. She underwent a left adrenalectomy, and the histopathology identified pheochromocytoma. Two years later, she had tumor recurrence with imaging studies showing multiple lung nodules. Following a wedge resection by video-assisted thoracoscopic surgery (VATS), histopathology was read as metastatic pheochromocytoma at one institution and metastatic ACC at another institution. She later presented to the National Institutes of Health (NIH) where the diagnosis of ACC was confirmed. Following her ACC diagnosis, she was treated with mitotane and pembrolizumab which were stopped due to side effects and progression of disease. She is currently receiving etoposide, doxorubicin, and cisplatin (EDP). This case highlights the importance of using a multi-disciplinary approach in patient care. Thorough evaluation of the tumor’s pathology and analysis of the patient’s genetic profile are necessary to obtain the correct diagnosis for the patient and can significantly influence the course of treatment.
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- 2020
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9. Kidney tumors associated with germline mutations of FH and SDHB show a CpG island methylator phenotype (CIMP).
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Christopher J Ricketts, J Keith Killian, Cathy D Vocke, Yonghong Wang, Maria J Merino, Paul S Meltzer, and W Marston Linehan
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Medicine ,Science - Abstract
Germline mutations within the Krebs cycle enzyme genes fumarate hydratase (FH) or succinate dehydrogenase (SDHB, SDHC, SDHD) are associated with an increased risk of aggressive and early metastasizing variants of renal cell carcinoma (RCC). These RCCs express significantly increased levels of intracellular fumarate or succinate that inhibit 2-oxoglutarate-dependent dioxygenases, such as the TET enzymes that regulate DNA methylation. This study evaluated the genome-wide methylation profiles of 34 RCCs from patients with RCC susceptibility syndromes and 11 associated normal samples using the Illumina HumanMethylation450 BeadChip. All the HLRCC (FH mutated) and SDHB-RCC (SDHB mutated) tumors demonstrated a distinct CpG island methylator phenotype (CIMP). HLRCC tumors demonstrated an extensive and relatively uniform level of hypermethylation that showed some correlation with tumor size. SDHB-RCC demonstrated a lesser and more varied pattern of hypermethylation that overlapped in part with the HLRCC hypermethylation. Combined methylation and mRNA expression analysis of the HLRCC tumors demonstrated hypermethylation and transcription downregulation of genes associated with the HIF pathway, HIF3A and CITED4, the WNT pathway, SFRP1, and epithelial-to-mesenchymal transition and MYC expression, OVOL1. These observations were confirmed in the TCGA CIMP-RCC tumors. A selected panel of probes could identify the CIMP tumors and differentiate between HLRCC and SDHB-RCC tumors. This panel accurately detected all CIMP-RCC tumors within the TCGA RCC cohort, identifying them as HLRCC -like, and could potentially be used to create a liquid biopsy-based screening tool. The CIMP signature in these aggressive tumors could provide both a useful biomarker for diagnosis and a target for novel therapies.
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- 2022
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10. KLF3 and PAX6 are candidate driver genes in late-stage, MSI-hypermutated endometrioid endometrial carcinomas
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Meghan L. Rudd, Nancy F. Hansen, Xiaolu Zhang, Mary Ellen Urick, Suiyuan Zhang, Maria J. Merino, National Institutes of Health Intramural Sequencing Center Comparative Sequencing Program, James C. Mullikin, Lawrence C. Brody, and Daphne W. Bell
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Medicine ,Science - Abstract
Endometrioid endometrial carcinomas (EECs) are the most common histological subtype of uterine cancer. Late-stage disease is an adverse prognosticator for EEC. The purpose of this study was to analyze EEC exome mutation data to identify late-stage-specific statistically significantly mutated genes (SMGs), which represent candidate driver genes potentially associated with disease progression. We exome sequenced 15 late-stage (stage III or IV) non-ultramutated EECs and paired non-tumor DNAs; somatic variants were called using Strelka, Shimmer, SomaticSniper and MuTect. Additionally, somatic mutation calls were extracted from The Cancer Genome Atlas (TCGA) data for 66 late-stage and 270 early-stage (stage I or II) non-ultramutated EECs. MutSigCV (v1.4) was used to annotate SMGs in the two late-stage cohorts and to derive p-values for all mutated genes in the early-stage cohort. To test whether late-stage SMGs are statistically significantly mutated in early-stage tumors, q-values for late-stage SMGs were re-calculated from the MutSigCV (v1.4) early-stage p-values, adjusting for the number of late-stage SMGs tested. We identified 14 SMGs in the combined late-stage EEC cohorts. When the 14 late-stage SMGs were examined in the TCGA early-stage data, only Krüppel-like factor 3 (KLF3) and Paired box 6 (PAX6) failed to reach significance as early-stage SMGs, despite the inclusion of enough early-stage cases to ensure adequate statistical power. Within TCGA, nonsynonymous mutations in KLF3 and PAX6 were, respectively, exclusive or nearly exclusive to the microsatellite instability (MSI)-hypermutated molecular subgroup and were dominated by insertions-deletions at homopolymer tracts. In conclusion, our findings are hypothesis-generating and suggest that KLF3 and PAX6, which encode transcription factors, are MSI target genes and late-stage-specific SMGs in EEC.
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- 2022
11. Macronodular adrenal hyperplasia masquerading as an upper pole renal mass
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Jeunice Owens-Walton, Sandeep Gurram, Maria J. Merino, W. Marston Linehan, and Mark W. Ball
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Macronodular adrenal hyperplasia ,Micronodular adrenal hyperplasia ,Upper pole renal mass ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Macronodular hyperplasia (MAH) of the adrenal gland is a rare disease usually presenting with Cushing Syndrome. Although usually readily apparent on imaging, an adrenal tumor in an asymptomatic patient may be mistaken for a renal tumor. We present a patient with combined macro- and micro-nodular adrenal hyperplasia masquerading as an upper pole renal mass. The patient underwent a robotic partial nephrectomy and partial adrenalectomy without complication.
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- 2021
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12. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations
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Fatima Karzai, David VanderWeele, Ravi A. Madan, Helen Owens, Lisa M. Cordes, Amy Hankin, Anna Couvillon, Erin Nichols, Marijo Bilusic, Michael L. Beshiri, Kathleen Kelly, Venkatesh Krishnasamy, Sunmin Lee, Min-Jung Lee, Akira Yuno, Jane B. Trepel, Maria J. Merino, Ryan Dittamore, Jennifer Marté, Renee N. Donahue, Jeffrey Schlom, Keith J. Killian, Paul S. Meltzer, Seth M. Steinberg, James L. Gulley, Jung-Min Lee, and William L. Dahut
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Durvalumab ,Olaparib ,mCRPC ,Abiraterone ,Enzalutamide ,Immunotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and Drug Administration for locally advanced or metastatic urothelial cancer and locally advanced, unresectable stage 3 non-small cell lung cancer. Olaparib, a poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) in select patients with metastatic castration-resistant prostate cancer (mCRPC). Data from other trials suggest there may be improved activity in men with DNA damage repair (DDR) mutations treated with checkpoint inhibitors. This trial evaluated durvalumab and olaparib in patients with mCRPC with and without somatic or germline DDR mutations. Methods Eligible patients had received prior enzalutamide and/or abiraterone. Patients received durvalumab 1500 mg i.v. every 28 days and olaparib 300 mg tablets p.o. every 12 h until disease progression or unacceptable toxicity. All patients had biopsies of metastatic lesions with an evaluation for both germline and somatic mutations. Results Seventeen patients received durvalumab and olaparib. Nausea was the only nonhematologic grade 3 or 4 toxicity occurring in > 1 patient (2/17). No patients were taken off trial for toxicity. Median radiographic progression-free survival (rPFS) for all patients is 16.1 months (95% CI: 4.5–16.1 months) with a 12-month rPFS of 51.5% (95% CI: 25.7–72.3%). Activity is seen in patients with alterations in DDR genes, with a median rPFS of 16.1 months (95% CI: 7.8–18.1 months). Nine of 17 (53%) patients had a radiographic and/or PSA response. Patients with fewer peripheral myeloid-derived suppressor cells and with alterations in DDR genes were more likely to respond. Early changes in circulating tumor cell counts and in both innate and adaptive immune characteristics were associated with response. Conclusions Durvalumab plus olaparib has acceptable toxicity, and the combination demonstrates efficacy, particularly in men with DDR abnormalities. Trial registration ClinicalTrials.gov identifier: NCT02484404.
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- 2018
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13. Succinate Mediates Tumorigenic Effects via Succinate Receptor 1: Potential for New Targeted Treatment Strategies in Succinate Dehydrogenase Deficient Paragangliomas
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Dieter M. Matlac, Katerina Hadrava Vanova, Nicole Bechmann, Susan Richter, Julica Folberth, Hans K. Ghayee, Guang-Bo Ge, Luma Abunimer, Robert Wesley, Redouane Aherrahrou, Margo Dona, Ángel M. Martínez-Montes, Bruna Calsina, Maria J. Merino, Markus Schwaninger, Peter M. T. Deen, Zhengping Zhuang, Jiri Neuzil, Karel Pacak, Hendrik Lehnert, and Stephanie M. J. Fliedner
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succinate receptor 1 ,SUCNR1 (GPR91) ,paraganglioma ,succinate ,SDHB gene ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Paragangliomas and pheochromocytomas (PPGLs) are chromaffin tumors associated with severe catecholamine-induced morbidities. Surgical removal is often curative. However, complete resection may not be an option for patients with succinate dehydrogenase subunit A-D (SDHx) mutations. SDHx mutations are associated with a high risk for multiple recurrent, and metastatic PPGLs. Treatment options in these cases are limited and prognosis is dismal once metastases are present. Identification of new therapeutic targets and candidate drugs is thus urgently needed. Previously, we showed elevated expression of succinate receptor 1 (SUCNR1) in SDHB PPGLs and SDHD head and neck paragangliomas. Its ligand succinate has been reported to accumulate due to SDHx mutations. We thus hypothesize that autocrine stimulation of SUCNR1 plays a role in the pathogenesis of SDHx mutation-derived PPGLs. We confirmed elevated SUCNR1 expression in SDHx PPGLs and after SDHB knockout in progenitor cells derived from a human pheochromocytoma (hPheo1). Succinate significantly increased viability of SUCNR1-transfected PC12 and ERK pathway signaling compared to control cells. Candidate SUCNR1 inhibitors successfully reversed proliferative effects of succinate. Our data reveal an unrecognized oncometabolic function of succinate in SDHx PPGLs, providing a growth advantage via SUCNR1.
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- 2021
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14. A Case Report of Sequential Use of a Yeast-CEA Therapeutic Cancer Vaccine and Anti-PD-L1 Inhibitor in Metastatic Medullary Thyroid Cancer
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Jaydira Del Rivero, Renee N. Donahue, Jennifer L. Marté, Ann W. Gramza, Marijo Bilusic, Myrna Rauckhorst, Lisa Cordes, Maria J. Merino, William L. Dahut, Jeffrey Schlom, James L. Gulley, and Ravi A. Madan
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medullary thyroid cancer ,CEA ,calcitonin ,immunotherapy ,PD-L1 inhibitor ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Medullary thyroid cancer (MTC) accounts for ~4% of all thyroid malignancies. MTC derives from the neural crest and secretes calcitonin (CTN) and carcinoembryonic antigen (CEA). Unlike differentiated thyroid cancer, MTC does not uptake iodine and I-131 RAI (radioactive iodine) treatment is ineffective. Patients with metastatic disease are candidates for FDA-approved agents with either vandetanib or cabozantinib; however, adverse effects limit their use. There are ongoing trials exploring the role of less toxic immunotherapies in patients with MTC. We present a 61-year-old male with the diagnosis of MTC and persistent local recurrence despite multiple surgeries. He was started on sunitinib, but ultimately its use was limited by toxicity. He then presented to the National Cancer Institute (NCI) and was enrolled on a clinical trial with heat-killed yeast-CEA vaccine (NCT01856920) and his calcitonin doubling time improved in 3 months. He then came off vaccine for elective surgery. After surgery, his calcitonin was rising and he enrolled on a phase I trial of avelumab, a programmed death-ligand 1 (PD-L1) inhibitor (NCT01772004). Thereafter, his calcitonin decreased > 40% on 5 consecutive evaluations. His tumor was subsequently found to express PD-L1. CEA-specific T cells were increased following vaccination, and a number of potential immune-enhancing changes were noted in the peripheral immunome over the course of sequential immunotherapy treatment. Although calcitonin declines do not always directly correlate with clinical responses, this response is noteworthy and highlights the potential for immunotherapy or sequential immunotherapy in metastatic or unresectable MTC.
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- 2020
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15. MRI-guided pelvic lymph node biopsy via transrectal approach in prostate cancer
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Christian Hague, Luke P. O'Connor, Alex Z. Wang, Patrick T. Gomella, Nitin K. Yerram, Maria J. Merino, and Peter A. Pinto
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Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Lymph node assessment in prostate cancer is most commonly performed at the time of radical prostatectomy. We present the case of pre-operative pelvic lymph node sampling with the use of MRI/TRUS fusion-guided biopsy at the time of prostate biopsy. Lymph node pathology revealed metastatic, poorly differentiated prostate cancer, concurrent with Gleason 4 + 5 disease showing perineural invasion. The use of MRI fusion guided biopsy for nodal sampling may be an effective method pre-operative staging and treatment planning for prostate adenocarcinoma. Keywords: MRI/TRUS fusion-guided biopsy, Lymph node biopsy, Prostate cancer, Pre-operative staging
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- 2020
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16. Incidental bladder cancers found on multiparametric MRI of the prostate gland: a single center experience
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Kareem N. Rayn, Graham R. Hale, Jonathan B. Bloom, Samuel A. Gold, Filipe L.F. Carvalho, Sherif Mehralivand, Marcin Czarniecki, Bradford J. Wood, Maria J. Merino, Peter Choyke, Barış Türkbey, Peter A. Pinto, and Piyush K. Agarwal
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
PURPOSE:In the era of multiparametric magnetic resonance imaging (mpMRI) of the prostate gland, incidental findings are occasionally discovered on imaging. We aimed to report our experience of detecting incidental bladder cancers on mpMRI of the prostate in asymptomatic patients without irritative voiding symptoms or microscopic or gross hematuria.METHODS:A retrospective review was performed on a prospectively maintained database of all men who underwent prostate mpMRI at our institution from 2012 to 2018. Patients who were found to have incidental bladder lesions were identified and baseline demographics, imaging and histopathologic data were recorded. All patients with incidental bladder lesion detection on mpMRI, not attributable to extension of prostate cancer, underwent cystoscopy in addition to a biopsy and/or transurethral resection of bladder tumor (TURBT) if warranted on cystoscopy.RESULTS:There were 3147 prostate mpMRIs performed during this period and 25 cases (0.8%) of incidental bladder lesions were detected. These patients did not have any presenting symptoms such as gross or microscopic hematuria to prompt bladder lesion workup. The largest diameter of incidentally discovered bladder lesions ranged from 0.4 cm to 1.7 cm. Of the 25 cases of incidental bladder lesions, five were suspected to be due to prostate cancer invasion into the bladder. Only two of these five patients underwent biopsy, which confirmed prostate adenocarcinoma in both cases. Of the 20 patients without suspected prostate cancer invasion of the bladder, four had no suspicious lesions on cystoscopy to warrant a biopsy. The remaining 16 patients had bladder lesions seen on cystoscopy and underwent a biopsy and/or TURBT. Three of these patients had benign features on pathology (urachal remnant, amyloidosis and inflammation) and the remaining 13 had stage Ta urothelial carcinoma. Seven of these patients had low-grade Ta tumors and six had high-grade Ta tumors. All patients were treated with standard management of TURBT with or without intravesical BCG. There have been no reported cases of recurrence or progression in any of the patients in our cohort at the median follow-up of 26 months (interquartile range,19–40 months).CONCLUSION:mpMRI of the prostate may yield incidental findings, such as small bladder tumors. Awareness of the possibility of incidental bladder lesions is important as 65% of lesions reported in the bladder, not attributable to extension of prostate cancer, proved to be bladder cancer. This may allow for early intervention for asymptomatic patients with undetected bladder cancer prior to disease progression.
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- 2018
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17. Multiparametric MRI for the detection of local recurrence of prostate cancer in the setting of biochemical recurrence after low dose rate brachytherapy
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Luca F. Valle, Matthew D. Greer, Joanna H. Shih, Tristan Barrett, Yan Mee Law, Andrew B. Rosenkrantz, Haytham Shebel, Akhil Muthigi, Daniel Su, Maria J. Merino, Bradford J. Wood, Peter A. Pinto, Andra V. Krauze, Aradhana Kaushal, Peter L. Choyke, Barış Türkbey, and Deborah E. Citrin
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
PURPOSE:Prostate multiparametric magnetic resonance imaging (mpMRI) has utility in detecting post-radiotherapy local recurrence. We conducted a multireader study to evaluate the diagnostic performance of mpMRI for local recurrence after low dose rate (LDR) brachytherapy.METHODS:A total of 19 patients with biochemical recurrence after LDR brachytherapy underwent 3T endorectal coil mpMRI with T2-weighted imaging, dynamic contrast-enhanced imaging (DCE) and diffusion-weighted imaging (DWI) with pathologic confirmation. Prospective reads by an experienced prostate radiologist were compared with reads from 4 radiologists of varying experience. Readers identified suspicious lesions and rated each MRI detection parameter. MRI-detected lesions were considered true-positive with ipsilateral pathologic confirmation. Inferences for sensitivity, specificity, positive predictive value (PPV), kappa, and index of specific agreement were made with the use of bootstrap resampling.RESULTS:Pathologically confirmed recurrence was found in 15 of 19 patients. True positive recurrences identified by mpMRI were frequently located in the transition zone (46.7%) and seminal vesicles (30%). On patient-based analysis, average sensitivity of mpMRI was 88% (standard error [SE], 3.5%). For highly suspicious lesions, specificity of mpMRI was 75% (SE, 16.5%). On lesion-based analysis, the average PPV was 62% (SE, 6.7%) for all lesions and 78.7% (SE, 10.3%) for highly suspicious lesions. The average PPV for lesions invading the seminal vesicles was 88.8% (n=13). The average PPV was 66.6% (SE, 5.8%) for lesions identified with T2-weighted imaging, 64.9% (SE, 7.3%) for DCE, and 70% (SE, 7.3%) for DWI.CONCLUSION:This series provides evidence that mpMRI after LDR brachytherapy is feasible with a high patient-based cancer detection rate. Radiologists of varying experience demonstrated moderate agreement in detecting recurrence.
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- 2018
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18. A Cascaded Deep Learning–Based Artificial Intelligence Algorithm for Automated Lesion Detection and Classification on Biparametric Prostate Magnetic Resonance Imaging
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Peter A. Pinto, Stephanie Harmon, Samira Masoudi, Dong Yang, Holger R. Roth, Deepak Kesani, Baris Turkbey, Daguang Xu, Thomas Sanford, Sherif Mehralivand, Bradford J. Wood, Maria J. Merino, Nathan Lay, Peter L. Choyke, and Ziyue Xu
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Male ,Lesion ,Prostate cancer ,Deep Learning ,Artificial Intelligence ,Prostate ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Segmentation ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,Lesion detection ,business.industry ,Deep learning ,Prostatic Neoplasms ,Cancer ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Artificial intelligence ,medicine.symptom ,business ,Algorithm ,Algorithms - Abstract
Rationale and objectives Prostate MRI improves detection of clinically significant prostate cancer; however, its diagnostic performance has wide variation. Artificial intelligence (AI) has the potential to assist radiologists in the detection and classification of prostatic lesions. Herein, we aimed to develop and test a cascaded deep learning detection and classification system trained on biparametric prostate MRI using PI-RADS for assisting radiologists during prostate MRI read out. Materials and Methods T2-weighted, diffusion-weighted (ADC maps, high b value DWI) MRI scans obtained at 3 Tesla from two institutions (n = 1043 in-house and n = 347 Prostate-X, respectively) acquired between 2015 to 2019 were used for model training, validation, testing. All scans were retrospectively reevaluated by one radiologist. Suspicious lesions were contoured and assigned a PI-RADS category. A 3D U-Net-based deep neural network was used to train an algorithm for automated detection and segmentation of prostate MRI lesions. Two 3D residual neural network were used for a 4-class classification task to predict PI-RADS categories 2 to 5 and BPH. Training and validation used 89% (n = 1290 scans) of the data using 5 fold cross-validation, the remaining 11% (n = 150 scans) were used for independent testing. Algorithm performance at lesion level was assessed using sensitivities, positive predictive values (PPV), false discovery rates (FDR), classification accuracy, Dice similarity coefficient (DSC). Additional analysis was conducted to compare AI algorithm's lesion detection performance with targeted biopsy results. Results Median age was 66 years (IQR = 60-71), PSA 6.7 ng/ml (IQR = 4.7-9.9) from in-house cohort. In the independent test set, algorithm correctly detected 111 of 198 lesions leading to 56.1% (49.3%-62.6%) sensitivity. PPV was 62.7% (95% CI 54.7%-70.7%) with FDR of 37.3% (95% CI 29.3%-45.3%). Of 79 true positive lesions, 82.3% were tumor positive at targeted biopsy, whereas of 57 false negative lesions, 50.9% were benign at targeted biopsy. Median DSC for lesion segmentation was 0.359. Overall PI-RADS classification accuracy was 30.8% (95% CI 24.6%-37.8%). Conclusion Our cascaded U-Net, residual network architecture can detect, classify cancer suspicious lesions at prostate MRI with good detection, reasonable classification performance metrics.
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- 2022
19. Prospective Evaluation of PI-RADS Version 2.1 for Prostate Cancer Detection and Investigation of Multiparametric MRI–derived Markers
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Enis C. Yilmaz, Joanna H. Shih, Mason J. Belue, Stephanie A. Harmon, Tim E. Phelps, Charisse Garcia, Lindsey A. Hazen, Antoun Toubaji, Maria J. Merino, Sandeep Gurram, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto, and Baris Turkbey
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Radiology, Nuclear Medicine and imaging - Published
- 2023
20. An MRI-based radiomics model to predict clear cell renal cell carcinoma growth rate classes in patients with von Hippel-Lindau syndrome
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Pouria Yazdian Anari, Nathan Lay, Nikhil Gopal, Aditi Chaurasia, Safa Samimi, Stephanie Harmon, Fatemeh Dehghani Firouzabadi, Maria J. Merino, Paul Wakim, Evrim Turkbey, Elizabeth C. Jones, Mark W. Ball, Baris Turkbey, W. Marston Linehan, and Ashkan A. Malayeri
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Adult ,Machine Learning ,von Hippel-Lindau Disease ,Radiological and Ultrasound Technology ,Urology ,Gastroenterology ,Humans ,Radiology, Nuclear Medicine and imaging ,Middle Aged ,Carcinoma, Renal Cell ,Magnetic Resonance Imaging ,Kidney Neoplasms ,Retrospective Studies - Abstract
Upfront knowledge of tumor growth rates of clear cell renal cell carcinoma in von Hippel-Lindau syndrome (VHL) patients can allow for a more personalized approach to either surveillance imaging frequency or surgical planning. In this study, we implement a machine learning algorithm utilizing radiomic features of renal tumors identified on baseline magnetic resonance imaging (MRI) in VHL patients to predict the volumetric growth rate category of these tumors.A total of 73 VHL patients with 173 pathologically confirmed Clear Cell Renal Cell Carcinoma (ccRCCs) underwent MRI at least at two different time points between 2015 and 2021. Each tumor was manually segmented in excretory phase contrast T1 weighed MRI and co-registered on pre-contrast, corticomedullary and nephrographic phases. Radiomic features and volumetric data from each tumor were extracted using the PyRadiomics library in Python (4544 total features). Tumor doubling time (DT) was calculated and patients were divided into two groups: DT = 1 year and DT 1 year. Random forest classifier (RFC) was used to predict the DT category. To measure prediction performance, the cohort was randomly divided into 100 training and test sets (80% and 20%). Model performance was evaluated using area under curve of receiver operating characteristic curve (AUC-ROC), as well as accuracy, F1, precision and recall, reported as percentages with 95% confidence intervals (CIs).The average age of patients was 47.2 ± 10.3 years. Mean interval between MRIs for each patient was 1.3 years. Tumors included in this study were categorized into 155 Grade 2; 16 Grade 3; and 2 Grade 4. Mean accuracy of RFC model was 79.0% [67.4-90.6] and mean AUC-ROC of 0.795 [0.608-0.988]. The accuracy for predicting DT classes was not different among the MRI sequences (P-value = 0.56).Here we demonstrate the utility of machine learning in accurately predicting the renal tumor growth rate category of VHL patients based on radiomic features extracted from different T1-weighted pre- and post-contrast MRI sequences.
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- 2022
21. Differential VHL Mutation Patterns in Bilateral Clear Cell RCC Distinguishes Between Independent Primary Tumors and Contralateral Metastatic Disease
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Cathy D. Vocke, Christopher J. Ricketts, Adam R. Metwalli, Peter A. Pinto, Rabindra Gautam, Mark Raffeld, Maria J. Merino, Mark W. Ball, and W. Marston Linehan
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Von Hippel-Lindau Tumor Suppressor Protein ,Urology ,Mutation ,Humans ,DNA Methylation ,Carcinoma, Renal Cell ,Article ,Kidney Neoplasms - Abstract
OBJECTIVE: To evaluate whether bilateral, multifocal clear cell renal cell carcinoma (ccRCC) patients can be differentiated by VHL mutation analysis into cases that represent either multiple independently arising primary tumors, or a single primary tumor which has spread ipsilaterally as well as to the contralateral kidney. The nature of kidney cancer multifocality outside of known hereditary syndromes is as yet poorly understood. MATERIALS AND METHODS: DNA from multiple tumors per patient were evaluated for somatic VHL gene mutation and hypermethylation. A subset of tumors with shared VHL mutations were analyzed with targeted, next-generation sequencing assays. RESULTS: This cohort contained 5 patients with multiple tumors that demonstrated a shared somatic VHL mutation consistent with metastatic spread including to the contralateral kidney. In several cases this was substantiated by additional shared somatic mutations in ccRCC-associated genes. In contrast, the remaining 14 patients with multiple tumors demonstrated unique, unshared VHL alterations in every analyzed tumor, consistent with independently arising kidney tumors. None of these latter patients showed any evidence of local spread or distant metastasis. CONCLUSION: The spectrum of VHL alterations within evaluated bilateral, multifocal ccRCC tumors from a single patient can distinguish between multiple independent tumor growth and metastasis. This can be performed using currently available clinical genetic tests and will improve the accuracy of patient diagnosis and prognosis, as well as informing appropriate management.
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- 2022
22. Supplementary Figure 2 from A Novel Germline Mutation in BAP1 Predisposes to Familial Clear-Cell Renal Cell Carcinoma
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James Brugarolas, W. Marston Linehan, Charis Eng, Patricia L.M. Dahia, Xian-Jin Xie, Chao Xing, Adam R. Metwalli, Maria J. Merino, Nick Grishin, Lisa Kinch, Lindsay Middelton, James Peterson, Christopher J. Ricketts, Cathy D. Vocke, Alana Christie, Andrea Pavia-Jimenez, Samuel Peña-Llopis, Jessica L. Mester, Laura S. Schmidt, and Megan N. Farley
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PDF file - 233K, VHL mutation status in some but not all tumors from Family NCI-1326.
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- 2023
23. Supplementary Figure Legend from A Novel Germline Mutation in BAP1 Predisposes to Familial Clear-Cell Renal Cell Carcinoma
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James Brugarolas, W. Marston Linehan, Charis Eng, Patricia L.M. Dahia, Xian-Jin Xie, Chao Xing, Adam R. Metwalli, Maria J. Merino, Nick Grishin, Lisa Kinch, Lindsay Middelton, James Peterson, Christopher J. Ricketts, Cathy D. Vocke, Alana Christie, Andrea Pavia-Jimenez, Samuel Peña-Llopis, Jessica L. Mester, Laura S. Schmidt, and Megan N. Farley
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PDF file - 104K
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- 2023
24. Supplementary Figure Legends from Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
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Brigitte C. Widemann, Jack F. Shern, John W. Glod, Paul S. Meltzer, Maria J. Merino, Frank M. Balis, Elizabeth Fox, Oxana Kapustina, Steven G. Waguespack, Maya Lodish, Seth M. Steinberg, Eva Dombi, Claudia Derse-Anthony, Haiyan Lei, Yuelin Zhu, Srivandana Akshintala, and Ira L. Kraft
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Legends for all included Supplementary Figures
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- 2023
25. Supplementary Figure 5 from Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
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Brigitte C. Widemann, Jack F. Shern, John W. Glod, Paul S. Meltzer, Maria J. Merino, Frank M. Balis, Elizabeth Fox, Oxana Kapustina, Steven G. Waguespack, Maya Lodish, Seth M. Steinberg, Eva Dombi, Claudia Derse-Anthony, Haiyan Lei, Yuelin Zhu, Srivandana Akshintala, and Ira L. Kraft
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Heat map of cell cycle gene expression. Gene expression was normalized and compared between the primary MTC, metastasis one, and metastasis two lesions from the whole transcriptome RNA-seq data. Purple indicates lower and yellow indicates higher expression. Values to generate colors are z-scores across each genes' relative transcript levels [log2(FPKM)].
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- 2023
26. Data from A Unique Spectrum of Somatic PIK3CA (p110α) Mutations Within Primary Endometrial Carcinomas
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Daphne W. Bell, Maria J. Merino, Dennis C. Sgroi, Andrew K. Godwin, Sarah Fogoros, Jessica C. Price, and Meghan L. Rudd
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Purpose: The goal of this study was to comprehensively define the incidence of mutations in all exons of PIK3CA in both endometrioid endometrial cancer (EEC) and nonendometrioid endometrial cancer (NEEC).Experimental Design: We resequenced all coding exons of PIK3CA and PTEN, and exons 1 and 2 of KRAS, from 108 primary endometrial tumors. Somatic mutations were confirmed by sequencing matched normal DNAs. The biochemical properties of a subset of novel PIK3CA mutations were determined by exogenously expressing wild type and mutant constructs in U2OS cells and measuring levels of AKTSer473 phosphorylation.Results: Somatic PIK3CA mutations were detected in 52.4% of 42 EECs and 33.3% of 66 NEECs. Half (29 of 58) of all nonsynonymous PIK3CA mutations were in exons 1–7 and half were in exons 9 and 20. The exons 1–7 mutations localized to the ABD, ABD-RBD linker and C2 domains of p110α. Within these regions, Arg88, Arg93, Gly106, Lys111, Glu365, and Glu453, were recurrently mutated; Arg88, Arg93, and Lys111 formed mutation hotspots. The p110α-R93W, -G106R, -G106V, -K111E, -delP449-L455, and -E453K mutants led to increased levels of phospho-AKTSer473 compared to wild-type p110α. Overall, 62% of exons 1–7 PIK3CA mutants and 64% of exons 9–20 PIK3CA mutants were activating; 72% of exon 1–7 mutations have not previously been reported in endometrial cancer.Conclusions: Our study identified a new subgroup of endometrial cancer patients with activating mutations in the amino-terminal domains of p110α; these patients might be appropriate for consideration in clinical trials of targeted therapies directed against the PI3K pathway. Clin Cancer Res; 17(6); 1331–40. ©2011 AACR.
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- 2023
27. Supplementary Figure 4 from Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
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Brigitte C. Widemann, Jack F. Shern, John W. Glod, Paul S. Meltzer, Maria J. Merino, Frank M. Balis, Elizabeth Fox, Oxana Kapustina, Steven G. Waguespack, Maya Lodish, Seth M. Steinberg, Eva Dombi, Claudia Derse-Anthony, Haiyan Lei, Yuelin Zhu, Srivandana Akshintala, and Ira L. Kraft
- Abstract
Weight-for-age and height-for-age growth curves. Male patient weights (A), heights (B) and female patient weights (C), and heights (D) were monitored during the follow up period. Patient weight-for-age and height-for-age values were compared to U.S. Center for Disease Control reference growth curves.
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- 2023
28. Supplementary Figure 3 from Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
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Brigitte C. Widemann, Jack F. Shern, John W. Glod, Paul S. Meltzer, Maria J. Merino, Frank M. Balis, Elizabeth Fox, Oxana Kapustina, Steven G. Waguespack, Maya Lodish, Seth M. Steinberg, Eva Dombi, Claudia Derse-Anthony, Haiyan Lei, Yuelin Zhu, Srivandana Akshintala, and Ira L. Kraft
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Doubling time of calcitonin and CEA for patient #12 was suggestive of progressive disease. Patient #12 experienced best response 434 days after starting vandetanib, with stable lesions in the thyroid bed (showed on T2-weighted MRI of the neck, A) and the mediastinum (showed on CT of the chest, B). In August 2016, the sum of longest diameter (per RECIST) of target lesions was consistent with SD (C,D) (note that not all target lesions are shown). Biomarker response in the two years prior (E) showed CEA doubling time 1.2 years (F) and calcitonin doubling time 1.67 years (G). Patient #12 was confirmed to have PD via RECIST February 2017.
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- 2023
29. Data from Sequential Prostate Magnetic Resonance Imaging in Newly Diagnosed High-risk Prostate Cancer Treated with Neoadjuvant Enzalutamide is Predictive of Therapeutic Response
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William L. Dahut, Peter A. Pinto, Baris Turkbey, Adam G. Sowalsky, James L. Gulley, Peter L. Choyke, Huihui Ye, Rosina T. Lis, Monique N. Williams, Amy Hankin, Anna Couvillon, Marijo Bilusic, Guinevere Chun, Nicolas T. Terrigino, John R. Bright, Nicole V. Carrabba, Lisa M. Cordes, David J. VanderWeele, Stephanie A. Harmon, Maria J. Merino, Joanna H. Shih, Ravi A. Madan, Scott Wilkinson, Stephanie M. Walker, and Fatima Karzai
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Purpose:For high-risk prostate cancer, standard treatment options include radical prostatectomy (RP) or radiotherapy plus androgen deprivation therapy (ADT). Despite definitive therapy, many patients will have disease recurrence. Imaging has the potential to better define characteristics of response and resistance. In this study, we evaluated prostate multiparametric MRI (mpMRI) before and after neoadjuvant enzalutamide plus ADT.Patients and Methods:Men with localized intermediate- or high-risk prostate cancer underwent a baseline mpMRI and mpMRI-targeted biopsy followed by a second mpMRI after 6 months of enzalutamide and ADT prior to RP. Specimens were sectioned in the same plane as mpMRI using patient-specific 3D-printed molds to permit mpMRI-targeted biopsies to be compared with the same lesion from the RP. Specimens were analyzed for imaging and histologic correlates of response.Results:Of 39 patients enrolled, 36 completed imaging and RP. Most patients (92%) had high-risk disease. Fifty-eight lesions were detected on baseline mpMRI, of which 40 (69%) remained measurable at 6-month follow-up imaging. Fifty-five of 59 lesions (93%) demonstrated >50% volume reduction on posttreatment mpMRI. Three of 59 lesions (5%) demonstrated growth in size at follow-up imaging, with two lesions increasing more than 3-fold in volume. On whole-mount pathology, 15 patients demonstrated minimal residual disease (MRD) of Conclusions:Low relative lesion volume at baseline mpMRI was predictive of pathologic response. A subset of patients had limited response. Selection of patients based on these metrics may improve outcomes in high-risk disease.
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- 2023
30. Data from Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
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Brigitte C. Widemann, Jack F. Shern, John W. Glod, Paul S. Meltzer, Maria J. Merino, Frank M. Balis, Elizabeth Fox, Oxana Kapustina, Steven G. Waguespack, Maya Lodish, Seth M. Steinberg, Eva Dombi, Claudia Derse-Anthony, Haiyan Lei, Yuelin Zhu, Srivandana Akshintala, and Ira L. Kraft
- Abstract
Purpose: Vandetanib is well-tolerated in patients with advanced medullary thyroid carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not been reported previously.Experimental Design: We monitored toxicities and disease status in patients taking vandetanib for hereditary, advanced MTC. Tumor samples were analyzed for molecular mechanisms of disease progression.Results: Seventeen patients [8 male, age 13 (9–17)* years] enrolled; 16 had a RET p.Met918Thr germline mutation. The duration of vandetanib therapy was 6.1 (0.1–9.7+)* years with treatment ongoing in 9 patients. Best response was partial response in 10, stable disease in 6, and progressive disease in one patient. Duration of response was 7.4 (0.6–8.7+)* and 4.9 (0.6–7.8+)* years in patients with PR and SD, respectively. Six patients died 2.0 (0.4–5.7)* years after progression. Median progression-free survival (PFS) was 6.7 years [95% confidence interval (CI): 2.3 years–undefined] and 5-year overall survival (OS) was 88.2% (95% CI: 60.6%–96.9%). Of 16 patients with a RET p.Met918Thr mutation, progression-free survival was 6.7 years (95% CI: 3.1–undefined) and 5-year overall survival was 93.8% (95% CI: 63.2%–99.1%). No patients terminated treatment because of toxicity. DNA sequencing of tissue samples (n = 11) identified an increase in copy number alterations across the genome as a potential mechanism of drug resistance [*median (range)].Conclusions: This study demonstrates that vandetanib is safe and results in sustained responses in children and adolescents with hereditary MTC. Our preliminary molecular data suggest that an increase in copy number abnormalities may be associated with tumor progression in hereditary MTC patients treated with vandetanib. Clin Cancer Res; 24(4); 753–65. ©2017 AACR.
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- 2023
31. Data from Vandetanib in Children and Adolescents with Multiple Endocrine Neoplasia Type 2B Associated Medullary Thyroid Carcinoma
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Frank M. Balis, Samuel A. Wells, Seth M. Steinberg, Eva Dombi, Maya Lodish, Maria J. Merino, Patricia O. Whitcomb, Alberta Aikin, Leigh Marcus, Meredith K. Chuk, Brigitte C. Widemann, and Elizabeth Fox
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Purpose: Medullary thyroid carcinoma (MTC) is a manifestation of multiple endocrine neoplasia type 2 (MEN2) syndromes caused by germline, activating mutations in the RET (REarranged during Transfection) proto-oncogene. Vandetanib, a VEGF and EGF receptor inhibitor, blocks RET tyrosine kinase activity and is active in adults with hereditary MTC.Experimental Design: We conducted a phase I/II trial of vandetanib for children (5–12 years) and adolescents (13–18 years) with MTC to define a recommended dose and assess antitumor activity. The starting dose was 100 mg/m2 administered orally, once daily, continuously for 28-day treatment cycles. The dose could be escalated to 150 mg/m2/d after two cycles. Radiographic response to vandetanib was quantified using RECIST (v1.0), biomarker response was measured by comparing posttreatment serum calcitonin and carcinoembryonic antigen (CEA) levels to baseline, and a patient-reported outcome was used to assess clinical benefit.Results: Sixteen patients with locally advanced or metastatic MTC received vandetanib for a median (range) 27 (2–52) cycles. Eleven patients remain on protocol therapy. Diarrhea was the primary dose-limiting toxicity. In subjects with M918T RET germline mutations (n = 15) the confirmed objective partial response rate was 47% (exact 95% confidence intervals, 21%–75%). Biomarker partial response was confirmed for calcitonin in 12 subjects and for CEA in 8 subjects.Conclusion: Using an innovative trial design and selecting patients based on target gene expression, we conclude that vandetanib 100 mg/m2/d is a well-tolerated and highly active new treatment for children and adolescents with MEN2B and locally advanced or metastatic MTC. Clin Cancer Res; 19(15); 4239–48. ©2013 AACR.
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- 2023
32. Supplementary Data from A Unique Spectrum of Somatic PIK3CA (p110α) Mutations Within Primary Endometrial Carcinomas
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Daphne W. Bell, Maria J. Merino, Dennis C. Sgroi, Andrew K. Godwin, Sarah Fogoros, Jessica C. Price, and Meghan L. Rudd
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Supplementary Figure S1; Supplementary Tables S1-S5.
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- 2023
33. Supplementary Figure Legend from Vandetanib in Children and Adolescents with Multiple Endocrine Neoplasia Type 2B Associated Medullary Thyroid Carcinoma
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Frank M. Balis, Samuel A. Wells, Seth M. Steinberg, Eva Dombi, Maya Lodish, Maria J. Merino, Patricia O. Whitcomb, Alberta Aikin, Leigh Marcus, Meredith K. Chuk, Brigitte C. Widemann, and Elizabeth Fox
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PDF file - 67K
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- 2023
34. Supplementary Data from Sequential Prostate Magnetic Resonance Imaging in Newly Diagnosed High-risk Prostate Cancer Treated with Neoadjuvant Enzalutamide is Predictive of Therapeutic Response
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William L. Dahut, Peter A. Pinto, Baris Turkbey, Adam G. Sowalsky, James L. Gulley, Peter L. Choyke, Huihui Ye, Rosina T. Lis, Monique N. Williams, Amy Hankin, Anna Couvillon, Marijo Bilusic, Guinevere Chun, Nicolas T. Terrigino, John R. Bright, Nicole V. Carrabba, Lisa M. Cordes, David J. VanderWeele, Stephanie A. Harmon, Maria J. Merino, Joanna H. Shih, Ravi A. Madan, Scott Wilkinson, Stephanie M. Walker, and Fatima Karzai
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Contains supplementary methods and 3 supplementary tables.
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- 2023
35. Supplementary Figure 2 from Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
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Brigitte C. Widemann, Jack F. Shern, John W. Glod, Paul S. Meltzer, Maria J. Merino, Frank M. Balis, Elizabeth Fox, Oxana Kapustina, Steven G. Waguespack, Maya Lodish, Seth M. Steinberg, Eva Dombi, Claudia Derse-Anthony, Haiyan Lei, Yuelin Zhu, Srivandana Akshintala, and Ira L. Kraft
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Doubling time of calcitonin and CEA during vandetanib therapy. Calcitonin and CEA slopes and doubling times were calculated from the change during the initial four months of vandetanib (A,B), from values the year before experiencing PD or the data cutoff (C,D) and in patients that experienced progressive disease (E).
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- 2023
36. Supplementary Figure 1b from Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
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Brigitte C. Widemann, Jack F. Shern, John W. Glod, Paul S. Meltzer, Maria J. Merino, Frank M. Balis, Elizabeth Fox, Oxana Kapustina, Steven G. Waguespack, Maya Lodish, Seth M. Steinberg, Eva Dombi, Claudia Derse-Anthony, Haiyan Lei, Yuelin Zhu, Srivandana Akshintala, and Ira L. Kraft
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Patients #2, #5, #10, #11, #13, #15, and #16 experienced durable SD or PR during the follow up period. Calcitonin and CEA are shown as percent change from baseline at the start of vandetanib therapy (left y-axis). Tumor size is the sum of longest diameter of lesions per RECISTv1.0 (right y-axis).
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- 2023
37. Data from Nm23-H1 Suppresses Metastasis by Inhibiting Expression of the Lysophosphatidic Acid Receptor EDG2
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Patricia S. Steeg, Chand Khanna, Seth M. Steinberg, Maria J. Merino, Emily Hua, William G. McDermott, Cari Graff-Cherry, Mary Albaugh, Eleazar Vega-Valle, Arnulfo Mendoza, and Christine E. Horak
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Nm23-H1 transcriptionally down-regulates expression of the lysophosphatidic acid receptor EDG2 and this down-regulation is critical for Nm23-H1–mediated motility suppression in vitro. We investigated the effect of altered EDG2 expression on Nm23-H1–mediated metastasis suppression in vivo. Clonal MDA-MB-435–derived tumor cell lines transfected with Nm23-H1 together with either a vector control or EDG2 had similar anchorage-dependent and anchorage-independent growth rates in vitro. However, a 45- and 300-fold inhibition of motility and invasion (P < 0.0001), respectively, was observed in Nm23-H1/vector lines, whereas coexpression of EDG2 restored activity to levels observed in the parental line. Using fluorescently labeled cells and ex vivo microscopy, the capacity of these cells to adhere, arrest, extravasate, and survive in the murine lung over a 24-h time course was measured. Only 5% of Nm23-H1/vector–transfected cells were retained in the murine lung 6 h following tail vein injection; coexpression of EDG2 enhanced retention 8- to 13-fold (P < 0.01). In a spontaneous metastasis assay, the primary tumor size of Nm23-H1/vector and Nm23-H1/EDG2 clones was not significantly different. However, restoration of EDG2 expression augmented the incidence of pulmonary metastasis from 51.9% to 90.4% (P = 2.4 × 10−5), comparable with parental MDA-MB-435 cells. To determine the relevance of this model system to human breast cancer, a cohort of breast carcinomas was stained for Nm23-H1 and EDG2 and a statistically significant inverse correlation between these two proteins was revealed (r = −0.73; P = 0.004). The data indicate that Nm23-H1 down-regulation of EDG2 is functionally important to suppression of tumor metastasis. [Cancer Res 2007;67(24):11751–9]
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- 2023
38. Supplementary Table 1, Figure Legend from Nm23-H1 Suppresses Metastasis by Inhibiting Expression of the Lysophosphatidic Acid Receptor EDG2
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Patricia S. Steeg, Chand Khanna, Seth M. Steinberg, Maria J. Merino, Emily Hua, William G. McDermott, Cari Graff-Cherry, Mary Albaugh, Eleazar Vega-Valle, Arnulfo Mendoza, and Christine E. Horak
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Supplementary Table 1, Figure Legend from Nm23-H1 Suppresses Metastasis by Inhibiting Expression of the Lysophosphatidic Acid Receptor EDG2
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- 2023
39. Supplementary Figure 1 from Nm23-H1 Suppresses Metastasis by Inhibiting Expression of the Lysophosphatidic Acid Receptor EDG2
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Patricia S. Steeg, Chand Khanna, Seth M. Steinberg, Maria J. Merino, Emily Hua, William G. McDermott, Cari Graff-Cherry, Mary Albaugh, Eleazar Vega-Valle, Arnulfo Mendoza, and Christine E. Horak
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Supplementary Figure 1 from Nm23-H1 Suppresses Metastasis by Inhibiting Expression of the Lysophosphatidic Acid Receptor EDG2
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- 2023
40. Deep learning‐based decision forest for hereditary clear cell renal cell carcinoma segmentation on MRI
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Nathan Lay, Pouria Yazdian Anari, Aditi Chaurasia, Fatemeh Dehghani Firouzabadi, Stephanie Harmon, Evrim Turkbey, Rabindra Gautam, Safa Samimi, Maria J. Merino, Mark W. Ball, William Marston Linehan, Baris Turkbey, and Ashkan A. Malayeri
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General Medicine - Published
- 2023
41. Why Does Magnetic Resonance Imaging-Targeted Biopsy Miss Clinically Significant Cancer?
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Nabila Khondakar, Christian Hague, Nitin Yerram, Michael Ahdoot, Peter A. Pinto, Baris Turkbey, Howard L. Parnes, Joanna Shih, Sherif Mehralivand, Michael Daneshvar, Maria J. Merino, Patrick T. Gomella, Andrew R Wilbur, Bradford J. Wood, Cheyenne Williams, Paul F. Pinsky, Sandeep Gurram, and Minhaj Siddiqui
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Image-Guided Biopsy ,Male ,medicine.medical_specialty ,medicine.diagnostic_test ,Missed Diagnosis ,business.industry ,Urology ,Prostate ,Cancer ,Prostatic Neoplasms ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Targeted biopsy ,Magnetic Resonance Imaging ,Article ,Biopsy ,medicine ,Humans ,Radiology ,business ,Systematic biopsy ,Aged ,Retrospective Studies - Abstract
PURPOSE: Multiple studies demonstrate MRI-targeted biopsy detects more clinically significant cancer than systematic biopsy, however some clinically significant cancers are detected by systematic biopsy only. While these events are rare, we sought to perform a retrospective analysis of these cases to ascertain the reasons that MRI-targeted biopsy missed clinically significant cancer, which was subsequently detected on systematic prostate biopsy. METHODS: Patients were enrolled in a prospective study comparing cancer detection rates by transrectal MRI-targeted fusion biopsy and systematic 12-core biopsy. Patients with an elevated PSA, abnormal digital rectal exam, or imaging findings concerning for prostate cancer underwent prostate MRI and subsequent MRI-targeted and systematic biopsy in the same setting. The subset of patients with grade group (GG) ≥3 cancer found on systematic biopsy and GG≤2 cancer (or no cancer) on MRI-targeted biopsy were classified as MRI-targeted biopsy misses. A retrospective analysis of the MRI and MRI-targeted biopsy real-time screen captures determined the cause of MRI-targeted biopsy miss. Multivariable logistic regression analysis compared baseline characteristics of patients with MRI-targeted biopsy misses to GG-matched patients whose clinically significant cancer was detected by MRI-targeted biopsy. RESULTS: Over the study period of 2007 to 2019, 2103 patients met study inclusion criteria and underwent combined MRI-targeted and systematic prostate biopsies. 41 (1.9%) men were classified as MRI-targeted biopsy misses. Most MRI-targeted biopsy misses were due to errors in lesion targeting (n=21, 51.2%), followed by MRI-invisible lesions (n=17, 40.5%), and MRI lesions missed by the radiologist (n=3, 7.1%). On logistic regression analysis, lower PI-RADS score was associated with having clinically significant cancer missed on MRI-targeted biopsy. CONCLUSION: While uncommon, most MRI-targeted biopsy misses are due to errors in lesions targeting, which highlights the importance of accurate co-registration and targeting when using software-based fusion platforms. Additionally, some patients will harbor MRI-invisible lesions which are un-targetable by MRI-targeted platforms. The presence of a low PI-RADS score despite a high PSA is suggestive of harboring an MRI-invisible lesion.
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- 2023
42. Multiple Recurrent Paraganglioma in a Pediatric Patient with Germline SDH-B Mutation
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Aidan McGowan, Julie Y. An, Sally Tanakchi, Mahir Maruf, Akhil Muthigi, Arvin George, Daniel Su, Maria J. Merino, W. Marston Linehan, Shawna L. Boyle, and Adam R. Metwalli
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Succinate dehydrogenase B mutation ,Paraganglioma ,Nephrectomy ,Adrenalectomy ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Magnetic Resonance Imaging (MRI) and fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) are recognized approaches for locating paragangliomas. Recently, gallium-68 DOTA-octreotate (DOTATATE) scans have shown promise detecting neuroendocrine tumors missed by FDG-PET and MRI. 13-year-old male with SDH-B mutation presented with symptoms of paraganglioma and elevated catecholamines. MRI did not demonstrate the T2 hyper intense signal typical of paraganglioma and pheochromocytoma; FDG-PET scan did not reveal increased foci of uptake. DOTATATE scan revealed a signal consistent only with residual adrenal tissue. Resection of the right adrenal bed revealed paraganglioma. Following surgery, no further symptoms were reported and biochemical tests normalized.
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- 2017
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43. Ipsilateral hemigland prostate biopsy may underestimate cancer burden in patients with unilateral mpMRI-visible lesions
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Tim E. Phelps, Enis C. Yilmaz, Stephanie A. Harmon, Mason J. Belue, Joanna H. Shih, Charisse Garcia, Lindsey A. Hazen, Antoun Toubaji, Maria J. Merino, Sandeep Gurram, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto, and Baris Turkbey
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Radiological and Ultrasound Technology ,Urology ,Gastroenterology ,Radiology, Nuclear Medicine and imaging - Published
- 2022
44. A diagnosis of Birt–Hogg–Dubé syndrome in individuals with Smith–Magenis syndrome: Recommendation for cancer screening
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Cathy D. Vocke, Leah R. Fleming, Anna M. Piskorski, Ali Amin, Chanika Phornphutkul, Suzanne de la Monte, Thierry Vilboux, Folami Duncan, Joan Pellegrino, Bonnie Braddock, Lindsay A. Middelton, Laura S. Schmidt, Maria J. Merino, Edward W. Cowen, Wendy J. Introne, W. Marston Linehan, and Ann C. M. Smith
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Genetics ,Genetics (clinical) ,Article - Abstract
We report a series of four unrelated adults with Smith-Magenis syndrome (SMS) and concomitant features of Birt-Hogg-Dubé (BHD) syndrome based upon haploinsufficiency for FLCN and characteristic renal cell carcinomas and/or evidence of cutaneous fibrofolliculomas. Three of the cases constitute the first known association of histopathologically verified characteristic BHD-associated renal tumors in adults with SMS; the fourth was identified to have histologically confirmed skin fibrofolliculomas. Molecular analysis documented second-hit FLCN mutations in two of the three cases with confirmed BHD renal pathology. These cases suggest the need to expand management recommendations for SMS to include kidney cancer surveillance starting at 20 years of age, as per the screening recommendations for BHD syndrome.
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- 2022
45. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
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Christopher J. Ricketts, Aguirre A. De Cubas, Huihui Fan, Christof C. Smith, Martin Lang, Ed Reznik, Reanne Bowlby, Ewan A. Gibb, Rehan Akbani, Rameen Beroukhim, Donald P. Bottaro, Toni K. Choueiri, Richard A. Gibbs, Andrew K. Godwin, Scott Haake, A. Ari Hakimi, Elizabeth P. Henske, James J. Hsieh, Thai H. Ho, Rupa S. Kanchi, Bhavani Krishnan, David J. Kwaitkowski, Wembin Lui, Maria J. Merino, Gordon B. Mills, Jerome Myers, Michael L. Nickerson, Victor E. Reuter, Laura S. Schmidt, C. Simon Shelley, Hui Shen, Brian Shuch, Sabina Signoretti, Ramaprasad Srinivasan, Pheroze Tamboli, George Thomas, Benjamin G. Vincent, Cathy D. Vocke, David A. Wheeler, Lixing Yang, William T. Kim, A. Gordon Robertson, Paul T. Spellman, W. Kimryn Rathmell, W. Marston Linehan, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Toshinori Hinoue, Peter W. Laird, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, onathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr., Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, and Armaz Mariamidze
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Biology (General) ,QH301-705.5 - Abstract
Summary: Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas
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- 2018
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46. Magnetic Resonance Imaging-Targeted and Systematic Biopsy for Detection of Grade Progression in Patients on Active Surveillance for Prostate Cancer
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Luke P. O'Connor, Stephanie Harmon, Baris Turkbey, Sherif Mehralivand, Nitin Yerram, Amir H. Lebastchi, Sandeep Gurram, Peter A. Pinto, Howard L. Parnes, Bradford J. Wood, Heather J. Chalfin, Lori Long, Alex Z. Wang, Johnathan Zeng, Maria J. Merino, Joanna Shih, Peter L. Choyke, and Michael Ahdoot
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Image-Guided Biopsy ,Male ,medicine.medical_specialty ,Biopsy ,Urology ,medicine.medical_treatment ,Article ,Prostate cancer ,Prostate ,medicine ,Humans ,In patient ,Prospective Studies ,Watchful Waiting ,Systematic biopsy ,Multiparametric Magnetic Resonance Imaging ,Aged ,medicine.diagnostic_test ,business.industry ,Prostatic Neoplasms ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Disease Progression ,Radiology ,Neoplasm Grading ,Intermediate risk ,business ,Watchful waiting - Abstract
PURPOSE: Active surveillance for patients with low and intermediate risk prostate cancers is becoming a more utilized option in recent years. However, the use of magnetic resonance imaging and imaging-targeted biopsy for monitoring grade progression has been poorly studied in this population. We aim to define the utility of magnetic resonance imaging-targeted biopsy and systematic biopsy in an active surveillance population. MATERIALS AND METHODS: Between July 2007 and January 2020, patients with diagnosed prostate cancer who elected active surveillance were monitored with prostate magnetic resonance imaging, imaging-targeted biopsy and standard systematic biopsy. Patients were eligible for surveillance if diagnosed with any volume Gleason grade 1 disease and select Gleason grade 2 disease. Grade progression (Gleason grade 1 to ≥2 disease and Gleason grade 2 to ≥3 disease) for each biopsy modality was measured at 2 years, 4 years and 6+ years. RESULTS: In total, 369 patients had both magnetic resonance imaging-targeted and systematic biopsy and were surveilled for at least 1 year. At 2 years, systematic biopsy, magnetic resonance imaging-targeted biopsy and combined biopsy (systematic+imaging-targeted) detected grade progression in 44 patients (15.9%), 73 patients (26.4%) and 90 patients (32.5%), respectively. Magnetic resonance imaging-targeted biopsy detected more cancer grade progression compared to systematic biopsy in both the low and intermediate risk populations (p
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- 2021
47. MRI Guided Fresh Tissue Procurement in Radical Prostatectomy Specimens: An Evolutionary Paradigm
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Raiza Z Freidlin, Marcial A Garmendia, Jonathan Krynitsky, Cody Bastian, Connor Schultz, Julian Custer, Sarah Young, Sherif Mehralivand, Maria J Merino, Vladimir A Valera, Peter Pinto, Baris Turkbey, Choyke L Peter, and Thomas J Pohida
- Abstract
PurposeThe aim of this work is to assess the feasibility of novel targeted methods for fresh tissue procurement that facilitate accurate identification of lesion location and tissue sample extraction in an excised prostate gland, while minimizing the tissue deformation or damage.Methods and ResultsProposed fresh tissue procurement methods are based on utilizing a custom 3D printed patient-specific prostate mold. In the semi-freehand method, the access cut is guided by a set of markers on the bottom of the mold that define the boundary of a lesion in two orthogonal directions. The procurement site is identified by palpation. In the guided cut with-locator card method the procurement sites are identified by a cutout in the locator cards inserted into the access cuts. The two approaches were utilized to procure >50 samples. In the biopsy needle method guiding channels were designed into the prostate mold to procure fresh tissue. This method was used 4 times. Finally, a mixed-reality biopsy needle method was developed for phantom testing.ConclusionsPreliminary results of fresh tissue procurement utilizing novel methods showed improve precision of obtaining cancerous fresh tissue for molecular and genomic cancer research compared to current methods which rely on surgical estimation of lesion location.
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- 2022
48. Natural history of small index lesions suspicious for prostate cancer on multiparametric MRI: recommendations for interval imaging follow-up
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Soroush Rais-Bahrami, Barış Türkbey, Ardeshir R. Rastinehad, Annerleim Walton-Diaz, Anthony N. Hoang, M. Minhaj Siddiqui, Lambros Stamatakis, Hong Truong, Jeffrey W. Nix, Srinivas Vourganti, Kinzya B. Grant, Maria J. Merino, Bradford J. Wood, Peter L. Choyke, and Peter A. Pinto
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
PURPOSEWe aimed to determine the natural history of small index lesions identified on multiparametric-magnetic resonance imaging (MP-MRI) of the prostate by evaluating lesion-specific pathology and growth on serial MP-MRI.MATERIALS AND METHODSWe performed a retrospective review of 153 patients who underwent a minimum of two MP-MRI sessions, on an institutional review board-approved protocol. Index lesion is defined as the lesion(s) with the highest cancer suspicion score based on initial MP-MRI of a patient, irrespective of size. Two study cohorts were identified: (1) patients with no index lesion or index lesion(s) ≤7 mm and (2) a subset with no index lesion or index lesion(s) ≤5 mm. Pathological analysis of the index lesions was performed following magnetic resonance/ultrasound fusion-guided biopsy. Growth rate of the lesions was calculated based on MP-MRI follow-up.RESULTSPatients with small index lesions measuring ≤7 mm (n=42) or a subset with lesions ≤5 mm (n=20) demonstrated either benign findings (86.2% and 87.5%, respectively) or low grade Gleason 6 prostate cancer (13.8% and 12.5%, respectively) on lesion-specific targeted biopsies. These lesions demonstrated no significant change in size (P = 0.93 and P = 0.36) over a mean imaging period of 2.31±1.56 years and 2.40±1.77 years for ≤7 mm and ≤5 mm index lesion thresholds, respectively. These findings held true on subset analyses of patients who had a minimum of two-year interval follow-up with MP-MRI.CONCLUSIONSmall index lesions of the prostate are pathologically benign lesions or occasionally low-grade cancers. Slow growth rate of these small index lesions on serial MP-MRI suggests a surveillance interval of at least two years without significant change.
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- 2014
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49. Imaging and pathology findings after an initial negative MRI-US fusion-guided and 12-core extended sextant prostate biopsy session
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Cheng William Hong,, Annerleim Walton-Diaz, Soroush Rais-Bahrami, Anthony N. Hoang,, Barış Türkbey,, Lambros Stamatakis,, Sheng Xu,, Hayet Amalou,, M. Minhaj Siddiqui,, Jeffrey W. Nix,, Srinivas Vourganti,, Maria J. Merino,, Peter L. Choyke,, Bradford J. Wood,, and Peter A. Pinto
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
PURPOSEA magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided prostate biopsy increases detection rates compared to an extended sextant biopsy. The imaging characteristics and pathology outcomes of subsequent biopsies in patients with initially negative MRI-US fusion biopsies are described in this study.MATERIALS AND METHODSWe reviewed 855 biopsy sessions of 751 patients (June 2007 to March 2013). The fusion biopsy consisted of two cores per lesion identified on multiparametric MRI (mpMRI) and a 12-core extended sextant transrectal US (TRUS) biopsy. Inclusion criteria were at least two fusion biopsy sessions, with a negative first biopsy and mpMRI before each.RESULTSThe detection rate on the initial fusion biopsy was 55.3%; 336 patients had negative findings. Forty-one patients had follow-up fusion biopsies, but only 34 of these were preceded by a repeat mpMRI. The median interval between biopsies was 15 months. Fourteen patients (41%) were positive for cancer on the repeat MRI-US fusion biopsy. Age, prostate-specific antigen (PSA), prostate volume, PSA density, digital rectal exam findings, lesion diameter, and changes on imaging were comparable between patients with negative and positive rebiopsies. Of the patients with positive rebiopsies, 79% had a positive TRUS biopsy before referral (P = 0.004). Ten patients had Gleason 3+3 disease, three had 3+4 disease, and one had 4+4 disease.CONCLUSIONIn patients with a negative MRI-US fusion prostate biopsy and indications for repeat biopsy, the detection rate of the follow-up sessions was lower than the initial detection rate. Of the prostate cancers subsequently found, 93% were low grade (≤3+4). In this low risk group of patients, increasing the follow-up time interval should be considered in the appropriate clinical setting.
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- 2014
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50. Lymphangitic Retroperitoneal Carcinomatosis Occurring From Metastatic Sarcomatoid Chromophobe Renal Cell Carcinoma
- Author
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Meghna Alimchandani, Karlena Lara, Maria Tsokos, W.M. Linehan, and Maria J. Merino
- Subjects
Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
A 45-year-old man with left renal mass underwent nephrectomy to reveal a 20-cm tumor diagnosed as sarcomatoid chromophobe renal cell carcinoma. Lymph node metastasis of chromophobe and sarcomatoid components, disseminated tumor in retroperitoneal fat, lymphatic vessels, and perirenal adipose tissue in lymphangitic carcinomatosis pattern were identified. Chromophobe epithelial cells were positive for epithelial membrane antigen, c-Kit, and cytokeratin 7; sarcomatoid cells were positive for CD10 and smooth muscle antigen with high proliferation index. Chromophobe epithelial cells had loss of heterozygosity in chromosomes 1p and 1q, whereas sarcomatoid cells had loss of heterozygosity in 3p, 1p, and 1q. In conclusion, sarcomatoid chromophobe renal cell carcinoma has aggressive biologic behavior and potential to metastasize in unusual patterns. Keywords: Renal cell carcinoma, Chromophobe, Sarcomatoid, Lymphangitic carcinomatosis, Lymph node metastasis
- Published
- 2014
- Full Text
- View/download PDF
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