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Most kidney cancers are metabolically dysfunctional1-4, but how this dysfunction affects cancer progression in humans is unknown. We infused 13C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-13C]acetate and [U-13C]glutamine infusions in patients, coupled with measurements of respiration in isolated human kidney and tumour mitochondria, reveal lower electron transport chain activity in ccRCCs that contributes to decreased oxidative and enhanced reductive TCA cycle labelling. However, ccRCC metastases unexpectedly have enhanced TCA cycle labelling compared with that of primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, whereas inhibiting electron transport chain complex I decreases metastasis. These findings in humans and mice indicate that metabolic properties and liabilities evolve during kidney cancer progression, and that mitochondrial function is limiting for metastasis but not growth at the original site.
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The broad range of disease aggressiveness together with imperfect screening, diagnostic, and treatment options in prostate cancer (PCa) makes medical decision-making complex. The primary goal of a multidisciplinary conference is to improve patient outcomes by combining evidence-based data and expert opinion to discuss optimal management, including for those patients with challenging presentations. The primary purpose of the genitourinary imaging specialist in the prostate cancer multidisciplinary conference is to use imaging findings to reduce uncertainty by answering clinical questions. In this review, we discuss the role and the opportunities for an imaging specialist to add value in the care of men with prostate cancer discussed at multidisciplinary conferences.
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BACKGROUND: Recent multicenter, multivendor MRI-based R2* vs. liver iron concentration (LIC) calibrations (i.e., MCMV calibrations) may facilitate broad clinical dissemination of R2*-based LIC quantification. However, these calibrations are based on a centralized offline R2* reconstruction, and their applicability with vendor-provided R2* maps is unclear. PURPOSE: To determine R2* ranges of agreement between the centralized and three MRI vendors' R2* reconstructions. STUDY TYPE: Prospective. SUBJECTS: Two hundred and seven subjects (mean age 37.6 ± 19.6 years; 117 male) with known or suspected iron overload from four academic medical centers. FIELD STRENGTH/SEQUENCE: Standardized multiecho spoiled gradient echo sequence at 1.5 T and 3.0 T for R2* mapping and a multiple spin-echo sequence at 1.5 T for LIC quantification. MRI vendors: GE Healthcare, Philips Healthcare, and Siemens Healthineers. ASSESSMENT: R2* maps were generated using both the centralized and vendor reconstructions, and ranges of agreement were determined. R2*-LIC linear calibrations were determined for each site, field strength, and reconstruction and compared with the MCMV calibrations. STATISTICAL TESTS: Bland-Altman analysis to determine ranges of agreement. Linear regression, analysis of covariance F tests, and Tukey's multiple comparison testing to assess reproducibility of calibrations across sites and vendors. A P value <0.05 was considered significant. RESULTS: The upper limits of R2* ranges of agreement were approximately 500, 375, and 330 s-1 for GE, Philips, and Siemens reconstructions, respectively, at 1.5 T and approximately 700 and 800 s-1 for GE and Philips, respectively, at 3.0 T. Within the R2* ranges of agreement, vendor R2*-LIC calibrations demonstrated high reproducibility (no significant differences between slopes or intercepts; P ≥ 0.06) and agreed with the MCMV calibrations (overlapping 95% confidence intervals). DATA CONCLUSION: Based on the determined upper limits, R2* measurements obtained from vendor-provided R2* maps may be reliably and practically used to quantify LIC less than approximately 8-13 mg/g using the MCMV calibrations and similar acquisition parameters as this study. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.
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Translocation renal cell carcinoma (tRCC) most commonly involves an ASPSCR1-TFE3 fusion, but molecular mechanisms remain elusive and animal models are lacking. Here, we show that human ASPSCR1-TFE3 driven by Pax8-Cre (a credentialed clear cell RCC driver) disrupted nephrogenesis and glomerular development, causing neonatal death, while the clear cell RCC failed driver, Sglt2-Cre, induced aggressive tRCC (as well as alveolar soft part sarcoma) with complete penetrance and short latency. However, in both contexts, ASPSCR1-TFE3 led to characteristic morphological cellular changes, loss of epithelial markers, and an epithelial-mesenchymal transition. Electron microscopy of tRCC tumors showed lysosome expansion, and functional studies revealed simultaneous activation of autophagy and mTORC1 pathways. Comparative genomic analyses encompassing an institutional human tRCC cohort (including a hitherto unreported SFPQ-TFEB fusion) and a variety of tumorgraft models (ASPSCR1-TFE3, PRCC-TFE3, SFPQ-TFE3, RBM10-TFE3, and MALAT1-TFEB) disclosed significant convergence in canonical pathways (cell cycle, lysosome, and mTORC1) and less established pathways such as Myc, E2F, and inflammation (IL-6/JAK/STAT3, interferon-γ, TLR signaling, systemic lupus, etc.). Therapeutic trials (adjusted for human drug exposures) showed antitumor activity of cabozantinib. Overall, this study provides insight into MiT/TFE-driven tumorigenesis, including the cell of origin, and characterizes diverse mouse models available for research.
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Carcinoma de Células Renales , Neoplasias Renales , Animales , Ratones , Recién Nacido , Humanos , Carcinoma de Células Renales/patología , Carcinogénesis/genética , Transformación Celular Neoplásica/genética , Modelos Animales de Enfermedad , Factores de Transcripción/genética , Genómica , Neoplasias Renales/patología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Translocación Genética , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Proteínas de Unión al ARN/genéticaRESUMEN
Experimental animal facilities can have a negative impact on the well-being of animals owing to confinement. To mitigate this, environmental enrichment (EE) is implemented confinement. The purpose of EE is to enhance the complexity of an animal's natural environment. The objective of this study was to identify the types of EE most enjoyed by dogs used in experimental research and housed in individual kennels. A total of six adult Beagle dogs, housed at the Laboratório de Quimioterapia Experimental em Parasitologia Veterinária (LQEPV) at the Universidade Federal Rural do Rio de Janeiro (UFRRJ) were included in the study. The EE tools used included Petball® toys, a grassy outdoor area, interaction with other dogs and with a team member, a "pool" made of plastic bottles, and dog's wet food ice cream. A team member assessed the usage of these tools every 5 min for a 30-min period, six times per day, one day per week, over the course of eight weeks. The study revealed that the grass area was the tool most commonly used for physical enrichment, accounting for 58% of the occurrences (p < 0.05). Social and food enrichment were enjoyed in second and third place, with 23% and 19% of occurrences, respectively. that the study findings suggest that dogs housed in individual kennels enjoy engaging in their natural behaviors.
Os animais de biotério podem viver em situações que afetem o seu bem-estar, como o confinamento. Um dos métodos que buscam para reduzir os impactos negativos é o Enriquecimento Ambiental (EA), o qual objetiva a promoção da complexidade do ambiente dos animais. Foi possível, com esta pesquisa, atingir o objetivo de identificar quais tipos de EA são mais aproveitados por cães utilizados em pesquisas experimentais que viviam em canis individuais. Foram utilizados seis cães adultos, Beagles, oriundos do Laboratório de Quimioterapia Experimental em Parasitologia Veterinária (LQEPV) da Universidade Federal Rural do Rio de Janeiro (UFRRJ). Como ferramentas de EA foram utilizados brinquedos Petball®, área de grama ao ar livre, interação com outros cães e com uma pessoa da equipe, "piscina" de garrafas plásticas e sorvete de ração úmida. Um membro da equipe avaliou o uso a cada 5 minutos, por período de 30 minutos (6 avaliações) por dia, um dia por semana ao longo de 8 semanas. O estudo revelou que a ferramenta mais usufruída pelos cães foi a área de grama através do enriquecimento físico, quantificado em 58% de ocorrência (p<0,05). Os enriquecimentos sociais e alimentar, foram usufruídos em segundo e terceiro lugar, com 23% e 19% de ocorrência, respectivamente. Pode-se concluir que os cães mantidos em canis individuais individualizados mais necessitam exercer seu comportamento natural específico, para que seu grau de bem-estar seja mantido em nível satisfatório e em consequência sua saúde mental.
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OBJECTIVE: This study aimed to develop a diagnostic model to estimate the distribution of small renal mass (SRM; ≤4 cm) histologic subtypes for patients with different demographic backgrounds and clear cell likelihood score (ccLS) designations. MATERIALS AND METHODS: A bi-institution retrospective cohort study was conducted where 347 patients (366 SRMs) underwent magnetic resonance imaging and received a ccLS before pathologic confirmation between June 2016 and November 2021. Age, sex, race, ethnicity, socioeconomic status, body mass index (BMI), and the ccLS were tabulated. The socioeconomic status for each patient was determined using the Area Deprivation Index associated with their residential address. The magnetic resonance imaging-derived ccLS assists in the characterization of SRMs by providing a likelihood of clear cell renal cell carcinoma (ccRCC). Pathological subtypes were grouped into four categories (ccRCC, papillary renal cell carcinoma, other renal cell carcinomas, or benign). Generalized estimating equations were used to estimate probabilities of the pathological subtypes across different patient subgroups. RESULTS: Race and ethnicity, BMI, and ccLS were significant predictors of histology (all P < 0.001). Obese (BMI, ≥30 kg/m 2 ) Hispanic patients with ccLS of ≥4 had the highest estimated rate of ccRCC (97.1%), and normal-weight (BMI, <25 kg/m 2 ) non-Hispanic Black patients with ccLS ≤2 had the lowest (0.2%). The highest estimated rates of papillary renal cell carcinoma were found in overweight (BMI, 25-30 kg/m 2 ) non-Hispanic Black patients with ccLS ≤2 (92.3%), and the lowest, in obese Hispanic patients with ccLS ≥4 (<0.1%). CONCLUSIONS: Patient race, ethnicity, BMI, and ccLS offer synergistic information to estimate the probabilities of SRM histologic subtypes.
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Carcinoma de Células Renales , Neoplasias Renales , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Estudios Retrospectivos , Persona de Mediana Edad , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patología , Anciano , Imagen por Resonancia Magnética/métodos , Adulto , Estudios de Cohortes , Riñón/diagnóstico por imagen , Riñón/patología , Índice de Masa Corporal , Anciano de 80 o más AñosRESUMEN
Multiparametric MRI-the most accurate imaging technique for detection of prostate cancer-has transformed the landscape of prostate cancer diagnosis by enabling targeted biopsies. In a targeted biopsy, tissue samples are obtained from suspicious regions identified at prebiopsy diagnostic MRI. The authors briefly compare the different strategies available for targeting an MRI-visible suspicious lesion, followed by a step-by-step description of the direct MRI-guided in-bore approach and an illustrated review of its application in challenging clinical scenarios. In this technique, direct visualization of the needle, needle guide, and needle trajectory during the procedure provides a precise and versatile strategy to accurately sample suspicious lesions, improving detection of clinically significant cancers. Published under a CC BY 4.0 license Test Your Knowledge questions for this article are available in the supplemental material.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos , Antígeno Prostático EspecíficoRESUMEN
INTRODUCTION: Testicular germ cell tumors are the most common malignancy in young adult males. Patients with metastatic disease receive standard of care chemotherapy followed by retroperitoneal lymph node dissection for residual masses >1cm. However, there is a need for better preoperative tools to discern which patients will have persistent disease after chemotherapy given low rates of metastatic germ cell tumor after chemotherapy. The purpose of this study was to use radiomics to predict which patients would have viable germ cell tumor or teratoma after chemotherapy at time of retroperitoneal lymph node dissection. PATIENTS AND METHODS: Patients with nonseminomatous germ cell tumor undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) between 2008 and 2019 were queried from our institutional database. Patients were included if prechemotherapy computed tomography (CT) scan and postchemotherapy imaging were available. Semiqualitative and quantitative features of residual masses and nodal regions of interest and radiomic feature extractions were performed by 2 board certified radiologists. Radiomic feature analysis was used to extract first order, shape, and second order statistics from each region of interest. Post-RPLND pathology was compared to the radiomic analysis using multiple t-tests. RESULTS: 45 patients underwent PC-RPLND at our institution, with the majority (28 patients) having stage III disease. 24 (53%) patients had teratoma on RPLND pathology, while 2 (4%) had viable germ cell tumor. After chemotherapy, 78%, 53%, and 33% of patients had cystic regions, fat stranding, and local infiltration present on imaging. After radiomic analysis, first order statistics mean, median, 90th percentile, and root mean squares were significant. Strong correlations were observed between these 4 features;a lower signal was associated with positive pathology at RPND. CONCLUSIONS: Testicular radiomics is an emerging tool that may help predict persistent disease after chemotherapy.
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Neoplasias de Células Germinales y Embrionarias , Teratoma , Neoplasias Testiculares , Masculino , Adulto Joven , Humanos , Radiómica , Resultado del Tratamiento , Espacio Retroperitoneal/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/cirugía , Escisión del Ganglio Linfático/métodos , Teratoma/diagnóstico por imagen , Teratoma/tratamiento farmacológico , Teratoma/cirugíaRESUMEN
BACKGROUND: Neoadjuvant therapy (NAT) emerged as the standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgery; however, surgery is morbid, and tools to predict resection margin status (RMS) and prognosis in the preoperative setting are needed. Radiomic models, specifically delta radiomic features (DRFs), may provide insight into treatment dynamics to improve preoperative predictions. METHODS: We retrospectively collected clinical, pathological, and surgical data (patients with resectable, borderline, locally advanced, and metastatic disease), and pre/post-NAT contrast-enhanced computed tomography (CT) scans from PDAC patients at the University of Texas Southwestern Medical Center (UTSW; discovery) and Humanitas Hospital (validation cohort). Gross tumor volume was contoured from CT scans, and 257 radiomics features were extracted. DRFs were calculated by direct subtraction of pre/post-NAT radiomic features. Cox proportional models and binary prediction models, including/excluding clinical variables, were constructed to predict overall survival (OS), disease-free survival (DFS), and RMS. RESULTS: The discovery and validation cohorts comprised 58 and 31 patients, respectively. Both cohorts had similar clinical characteristics, apart from differences in NAT (FOLFIRINOX vs. gemcitabine/nab-paclitaxel; p < 0.05) and type of surgery resections (pancreatoduodenectomy, distal or total pancreatectomy; p < 0.05). The model that combined clinical variables (pre-NAT carbohydrate antigen (CA) 19-9, the change in CA19-9 after NAT (∆CA19-9), and resectability status) and DRFs outperformed the clinical feature-based models and other radiomics feature-based models in predicting OS (UTSW: 0.73; Humanitas: 0.66), DFS (UTSW: 0.75; Humanitas: 0.64), and RMS (UTSW 0.73; Humanitas: 0.69). CONCLUSIONS: Our externally validated, predictive/prognostic delta-radiomics models, which incorporate clinical variables, show promise in predicting the risk of predicting RMS in NAT-treated PDAC patients and their OS or DFS.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante , Estudios Retrospectivos , Márgenes de Escisión , Radiómica , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugíaRESUMEN
Purpose: To develop and validate a semisupervised style transfer-assisted deep learning method for automated segmentation of the kidneys using multiphase contrast-enhanced (MCE) MRI acquisitions. Materials and Methods: This retrospective, Health Insurance Portability and Accountability Act-compliant, institutional review board-approved study included 125 patients (mean age, 57.3 years; 67 male, 58 female) with renal masses. Cohort 1 consisted of 102 coronal T2-weighted MRI acquisitions and 27 MCE MRI acquisitions during the corticomedullary phase. Cohort 2 comprised 92 MCE MRI acquisitions (23 acquisitions during four phases each, including precontrast, corticomedullary, early nephrographic, and nephrographic phases). The kidneys were manually segmented on T2-weighted images. A cycle-consistent generative adversarial network (CycleGAN) was trained to generate anatomically coregistered synthetic corticomedullary style images using T2-weighted images as input. Synthetic images for precontrast, early nephrographic, and nephrographic phases were then generated using the synthetic corticomedullary images as input. Mask region-based convolutional neural networks were trained on the four synthetic phase series for kidney segmentation using T2-weighted masks. Segmentation performance was evaluated in a different cohort of 20 originally acquired MCE MRI examinations by using Dice and Jaccard scores. Results: The CycleGAN network successfully generated anatomically coregistered synthetic MCE MRI-like datasets from T2-weighted acquisitions. The proposed deep learning approach for kidney segmentation achieved high mean Dice scores in all four phases of the original MCE MRI acquisitions (0.91 for precontrast, 0.92 for corticomedullary, 0.91 for early nephrographic, and 0.93 for nephrographic). Conclusion: The proposed deep learning approach achieved high performance in kidney segmentation on different MCE MRI acquisitions.Keywords: Kidney Segmentation, Generative Adversarial Network, CycleGAN, Convolutional Neural Network, Transfer Learning Supplemental material is available for this article. Published under a CC BY 4.0 license.
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BACKGROUND: Bosniak classification version 2019 includes cystic masses in class II and IIF based partly on their hyperintense appearance at T1-weighted MRI. The prevalence of malignancy in non-enhancing heterogeneously T1-hyperintense masses is unknown, nor whether the pattern of T1 hyperintensity affects malignancy likelihood. PURPOSE: To determine the malignancy proportion among six patterns of T1 hyperintensity within non-enhancing cystic renal masses. METHODS: This retrospective, single-institution study included 72 Bosniak class II and IIF, non-enhancing, T1-hyperintense cystic renal masses. Diagnosis was confirmed by histopathology or by follow-up imaging demonstrating 5-year size and morphologic stability, decreased in size by ≥ 30%, resolution, or Bosniak down-classification. Six patterns of T1 hyperintensity were pre-defined: homogeneous (pattern A), fluid-fluid level (pattern B), peripherally markedly T1-hyperintense (pattern C), containing a T1-hyperintense non-enhancing nodule (pattern D), peripherally T1-hypointense (pattern E), and heterogeneously T1-hyperintense without a distinct pattern (pattern F). Three readers independently assigned each mass to a pattern. Individual and mean malignancy proportion were determined. Mann-Whitney test and Fischer's exact test compared the likelihood of malignancy between patterns. Inter-reader agreement was analyzed with Gwet's agreement coefficient (AC). RESULTS: Among 72 masses, the mean number of masses assigned was 11 (15%) to pattern A, 21 (29%) to pattern B, 6 (8%) to pattern C, 7 (10%) to pattern D, 5 (7%) to pattern E, and 22 (31%) to pattern F. Five of 72 masses (7%) were malignant; none was assigned pattern A, B, or D. Mean malignancy proportion was 5% (0/9, 1/6, and 0/4) for pattern C, 13% (0/4, 1/3, and 1/7) for pattern E, and 18% (5/20, 3/21, and 4/25) for pattern F. Malignant masses were more likely assigned to pattern E or F (p = 0.003-0.039). Inter-reader agreement was substantial (Gwet's AC: 0.68). CONCLUSION: Bosniak version 2019 class IIF masses that are non-enhancing and heterogeneously T1-hyperintense with a fluid-fluid level are likely benign. Those that are non-enhancing and heterogeneously T1-hyperintense without a distinct pattern have a malignancy proportion up to 25% (5/20).
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Carcinoma de Células Renales , Enfermedades Renales Quísticas , Neoplasias Renales , Humanos , Estudios Retrospectivos , Enfermedades Renales Quísticas/diagnóstico por imagen , Enfermedades Renales Quísticas/patología , Riñón/patología , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patologíaRESUMEN
Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR. We systematically evaluated patients with RCC at UT Southwestern Medical Center (UTSW) Kidney Cancer Program (KCP) from July 2005 to March 2020. We queried Kidney Cancer Explorer (KCE), a data portal with clinical, pathological, and experimental genomic data. Patients were included in the study based on mention of "hemoptysis" in clinical documentation, if they had a previous bronchoscopy, or had undergone SAbR to any site within the chest. Two hundred and thirty four patients met query criteria and their records were individually reviewed. We identified 10 patients who developed LTH. Of these, 4 had LTH as an immediate procedural complication whilst the remaining 6 had prior SAbR to ultra-central (UC; abutting the central bronchial tree) metastases. These 6 patients had a total of 10 lung lesions irradiated (UC, 8; central 1, peripheral 1), with a median total cumulative SAbR dose of 38 Gray (Gy/ lesion) (range: 25-50 Gy). Other risk factors included intrathoracic disease progression (n = 4, 67%), concurrent anticoagulant therapy (n = 1, 17%) and concurrent systemic therapy (n = 4, 67%). Median time to LTH from first SAbR was 26 months (range: 8-61 months). Considering that 130 patients received SAbR to a chest lesion during the study period, the overall incidence of LTH following SAbR was 4.6% (6/130). The patient population that received SAbR (n = 130) was at particularly high risk for complications, with 67 (52%) having two or more chest metastaes treated, and 29 (22%) receiving SAbR to three or more lesions. Overall, the risk of LTH following SAbR to a central or UC lesion was 10.5% (6/57). In conclusion, SAbR of RCC metastases located near the central bronchial tree may increase the risk of LTH.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Pulmonares , Radiocirugia , Humanos , Carcinoma de Células Renales/secundario , Neoplasias Pulmonares/cirugía , Neoplasias Renales/patología , Radiocirugia/efectos adversosRESUMEN
BACKGROUND: Most renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited. OBJECTIVE: To investigate whether SAbR is effective in the management of primary RCCs. DESIGN, SETTING, AND PARTICIPANTS: Patients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 mm/yr on active surveillance) and pathologic evidence of tumor response at 1 yr. Secondary endpoints included LC by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), safety, and preservation of kidney function. Exploratory tumor cell-enriched spatial protein and gene expression analysis were conducted on pre- and post-treatment biopsy samples. RESULTS AND LIMITATIONS: Target accrual was reached with the enrollment of 16 ethnically diverse patients. Radiographic LC at 1 yr was observed in 94% of patients (15/16; 95% confidence interval: 70, 100), and this was accompanied by pathologic evidence of tumor response (hyalinization, necrosis, and reduced tumor cellularity) in all patients. By RECIST, 100% of the sites remained without progression at 1 yr. The median pretreatment growth rate was 0.8 cm/yr (interquartile range [IQR]: 0.3, 1.4), and the median post-treatment growth rate was 0.0 cm/yr (IQR: -0.4, 0.1, p < 0.002). Tumor cell viability decreased from 4.6% to 0.7% at 1 yr (p = 0.004). With a median follow-up of 36 mo for censored patients, the disease control rate was 94%. SAbR was well tolerated with no grade ≥2 (acute or late) toxicities. The average glomerular filtration rate declined from a baseline of 65.6 to 55.4 ml/min at 1 yr (p = 0.003). Spatial protein and gene expression analyses were consistent with the induction of cellular senescence by radiation. CONCLUSIONS: This clinical trial adds to the growing body of evidence suggesting that SAbR is effective for primary RCC supporting its evaluation in comparative phase 3 clinical trials. PATIENT SUMMARY: In this clinical trial, we investigated a noninvasive treatment option of stereotactic radiation therapy for the treatment of primary kidney cancer and found that it was safe and effective.
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Carcinoma de Células Renales , Neoplasias Renales , Radiocirugia , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Radiocirugia/efectos adversos , Radiocirugia/métodos , Estudios Prospectivos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Resultado del TratamientoRESUMEN
[This corrects the article DOI: 10.3233/KCA-210117.].
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Most kidney cancers display evidence of metabolic dysfunction1-4 but how this relates to cancer progression in humans is unknown. We used a multidisciplinary approach to infuse 13C-labeled nutrients during surgical tumour resection in over 70 patients with kidney cancer. Labeling from [U-13C]glucose varies across cancer subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumours. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic slices cultured ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with respiratory flux of mitochondria isolated from kidney and tumour tissue, reveal primary defects in mitochondrial function in human ccRCC. However, ccRCC metastases unexpectedly have enhanced labeling of TCA cycle intermediates compared to primary ccRCCs, indicating a divergent metabolic program during ccRCC metastasis in patients. In mice, stimulating respiration in ccRCC cells is sufficient to promote metastatic colonization. Altogether, these findings indicate that metabolic properties evolve during human kidney cancer progression, and suggest that mitochondrial respiration may be limiting for ccRCC metastasis but not for ccRCC growth at the site of origin.
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Chemical exchange saturation transfer (CEST) MRI has gained recognition as a valuable addition to the molecular imaging and quantitative biomarker arsenal, especially for characterization of brain tumors. There is also increasing interest in the use of CEST-MRI for applications beyond the brain. However, its translation to body oncology applications lags behind those in neuro-oncology. The slower migration of CEST-MRI to non-neurologic applications reflects the technical challenges inherent to imaging of the torso. In this review, we discuss the application of CEST-MRI to oncologic conditions of the breast and torso (i.e., body imaging), emphasizing the challenges and potential solutions to address them. While data are still limited, reported studies suggest that CEST signal is associated with important histology markers such as tumor grade, receptor status, and proliferation index, some of which are often associated with prognosis and response to therapy. However, further technical development is still needed to make CEST a reliable clinical application for body imaging and establish its role as a predictive and prognostic biomarker.
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Neoplasias Encefálicas , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Neoplasias Encefálicas/patología , Encéfalo/patología , Pronóstico , Imagen MolecularRESUMEN
Background MRI is a standard of care tool to measure liver iron concentration (LIC). Compared with regulatory-approved R2 MRI, R2* MRI has superior speed and is available in most MRI scanners; however, the cross-vendor reproducibility of R2*-based LIC estimation remains unknown. Purpose To evaluate the reproducibility of LIC via single-breath-hold R2* MRI at both 1.5 T and 3.0 T with use of a multicenter, multivendor study. Materials and Methods Four academic medical centers using MRI scanners from three different vendors (three 1.5-T scanners, one 2.89-T scanner, and two 3.0-T scanners) participated in this prospective cross-sectional study. Participants with known or suspected liver iron overload were recruited to undergo multiecho gradient-echo MRI for R2* mapping at 1.5 T and 3.0 T (2.89 T or 3.0 T) on the same day. R2* maps were reconstructed from the multiecho images and analyzed at a single center. Reference LIC measurements were obtained with a commercial R2 MRI method performed using standardized 1.5-T spin-echo imaging. R2*-versus-LIC calibrations were generated across centers and field strengths using linear regression and compared using F tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic performance of R2* MRI in the detection of clinically relevant LIC thresholds. Results A total of 207 participants (mean age, 38 years ± 20 [SD]; 117 male participants) were evaluated between March 2015 and September 2019. A linear relationship was confirmed between R2* and LIC. All calibrations within the same field strength were highly reproducible, showing no evidence of statistically significant center-specific differences (P > .43 across all comparisons). Calibrations for 1.5 T and 3.0 T were generated, as follows: for 1.5 T, LIC (in milligrams per gram [dry weight]) = -0.16 + 2.603 × 10-2 R2* (in seconds-1); for 2.89 T, LIC (in milligrams per gram) = -0.03 + 1.400 × 10-2 R2* (in seconds-1); for 3.0 T, LIC (in milligrams per gram) = -0.03 + 1.349 × 10-2 R2* (in seconds-1). Liver R2* had high diagnostic performance in the detection of clinically relevant LIC thresholds (area under the ROC curve, >0.98). Conclusion R2* MRI enabled accurate and reproducible quantification of liver iron overload over clinically relevant ranges of liver iron concentration (LIC). The data generated in this study provide the necessary calibrations for broad clinical dissemination of R2*-based LIC quantification. ClinicalTrials.gov registration no.: NCT02025543 © RSNA, 2022 Online supplemental material is available for this article.
Asunto(s)
Sobrecarga de Hierro , Hierro , Masculino , Humanos , Adulto , Hierro/análisis , Reproducibilidad de los Resultados , Estudios Prospectivos , Estudios Transversales , Hígado/química , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: The prostatic apex is the most frequent location of positive surgical margin (PSM) after surgery. Data regarding the ability of multiparametric magnetic resonance imaging (mpMRI) to prospectively identify men at risk for apical PSMs (aPSMs) using a structured report are lacking. OBJECTIVES: The aims of the study are to determine and to compare the rate of aPSM in men with versus without prospectively flagged at-risk prostate lesions during clinical mpMRI interpretation using whole-mount histopathology as the reference standard. METHODS: This single-center, retrospective study of prospectively collected data included treatment-naive men with abnormal 3T mpMRI (PI-RADS v2 score ≥3) between January 2016 and December 2018 followed by surgery. During routine clinical interpretation, radiologists flagged prostate lesions abutting the apical most gland and/or encircling the distal most prostatic urethra using standardized language available as a "pick list" option in the structured report. Logistic regression was used to compare the rate of PSM in 2 groups (flagged vs nonflagged men). Propensity score covariate adjustment corrected for potential selection bias according to age, prostate-specific antigen (PSA), PSA density, grade group, and pT stage. The estimate was further adjusted by including surgeon as a covariate. RESULTS: A total of 428 men were included. A statistically significant higher proportion of aPSMs was noted in flagged (56% [51/91]) compared with nonflagged apical lesions (31% [105/337]; adjusted odds ratio, 2.5; 95% confidence interval, 1.6-4.1; P < 0.01). The difference in aPSM between both groups also varied according to the surgeon performing the RP. Prostate-specific antigen, PSA density, lesion size, apical location, Prostate Imaging Reporting & Data System score, grade group, pT stage, and surgeon's experience were associated with higher PSM rate. Biochemical recurrence, defined as PSA greater than 0.2 ng/mL on 2 measurements after RP, was significantly associated with PSM status (propensity score adjusted odds ratio, 3.1; 95% confidence interval, 1.8-5.3; P < 0.0001); however, patients flagged by radiologists did not have a significant difference in biochemical recurrence rates as compared with nonflagged patients ( P = 0.11). CONCLUSIONS: Standard language built into structured reports for mpMRI of the prostate helps identify preoperatively patients at risk for aPSM. CLINICAL IMPACT: Multiparametric MRI is able to identify patients at increased risk for aPSM, and this information can be conveyed in a structured report to urologists, facilitating patient counseling and treatment decisions.