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Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, we review the epigenetics of sexual differentiation and its effect on cancer hallmark pathways throughout life. Specifically, we will touch on how sex differences in metabolism, immunity, pluripotency, and tumor suppressor functions are patterned through the epigenetic effects of imprinting, sex chromosome complement, X inactivation, genes escaping X inactivation, sex hormones, and life history.
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Epigênese Genética , Neoplasias , Caracteres Sexuais , Humanos , Feminino , Neoplasias/genética , Masculino , Animais , Inativação do Cromossomo X , Hormônios Esteroides Gonadais/metabolismo , Impressão GenômicaRESUMO
An overview of the role of glycosylation in prostate cancer (PCa) development and progression is presented, focusing on recent advancements in defining the N-glycome through glycomic profiling and glycoproteomic methodologies. Glycosylation is a common post-translational modification typified by oligosaccharides attached N-linked to asparagine or O-linked to serine or threonine on carrier proteins. These attached sugars have crucial roles in protein folding and cellular recognition processes, such that altered glycosylation is a hallmark of cancer pathogenesis and progression. In the past decade, advancements in N-glycan profiling workflows using Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) technology have been applied to define the spatial distribution of glycans in PCa tissues. Multiple studies applying N-glycan MALDI-MSI to pathology-defined PCa tissues have identified significant alterations in N-glycan profiles associated with PCa progression. N-glycan compositions progressively increase in number, and structural complexity due to increased fucosylation and sialylation. Additionally, significant progress has been made in defining the glycan and glycopeptide compositions of prostatic-derived glycoproteins like prostate-specific antigen in tissues and biofluids. The glycosyltransferases involved in these changes are potential drug targets for PCa, and new approaches in this area are summarized. These advancements will be discussed in the context of the further development of clinical diagnostics and therapeutics targeting glycans and glycoproteins associated with PCa progression. Integration of large scale spatial glycomic data for PCa with other spatial-omic methodologies is now feasible at the tissue and single-cell levels.
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Polissacarídeos , Neoplasias da Próstata , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Glicosilação , Humanos , Masculino , Polissacarídeos/metabolismo , Glicômica/métodos , Glicoproteínas/metabolismo , Biomarcadores Tumorais/metabolismo , Líquidos Corporais/metabolismo , Líquidos Corporais/química , Processamento de Proteína Pós-Traducional , Animais , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions for the 2024 update to the guidelines with regard to initial risk stratification, initial management of very-low-risk disease, and the treatment of nonmetastatic recurrence.
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Segunda Neoplasia Primária , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Medição de RiscoRESUMO
Prostate-specific membrane antigen-positron emission tomography (PSMA-PET) is transforming the management of patients with prostate cancer. In appropriately selected patients, PSMA-PET offers superior sensitivity and specificity compared to conventional imaging (e.g., computed tomography and bone scintigraphy) as well as choline and fluciclovine PET, with the added benefit of consolidating bone and soft tissue evaluation into a single study. Despite being a newly available imaging tool, PSMA-PET has established indications, interpretation guidelines, and reporting criteria, which will be reviewed. The prostate cancer care team, from imaging specialists to those delivering treatment, should have knowledge of physiologic PSMA radiotracer uptake, patterns of disease spread, and the strengths and limitations of PSMA-PET. In this review, current and emerging applications of PSMA-PET, including appropriateness use criteria as well as image interpretation and pitfalls, will be provided with an emphasis on clinical implications.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioisótopos de Gálio , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Tomografia por Emissão de PósitronsRESUMO
Our objective was to identify variations in gene expression that could help elucidate the pathways for the development of prostate cancer (PCa) in men with Benign Prostatic Hyperplasia (BPH). We included 98 men with BPH, a positive prostate MRI (Prostate Imaging Reporting and Data System; PIRADS ≥ 4), and a negative biopsy from November 2014 to January 2018. RNA sequencing (RNA-Seq) was performed on tissue cores from the MRI lesion and a geographically distant region (two regions per patient). All patients were followed for at least three years to identify who went on to develop PCa. We compared the gene expressions of those who did not develop PCa ("BPH-only") vs. those who did ("BPH/PCa"). Then, we identified the subset of men with BPH who had the highest American Urological Association (AUA) symptom scores ("symptomatic BPH") and compared their gene expression to the BPH/PCa group. At a median follow-up of 47.5 months, 15 men had developed PCa while 83 did not. We compared gene expressions of 14 men with symptomatic BPH (AUAss ≥ 18) vs. 15 with BPH/PCa. We found two clusters of genes, suggesting the two groups had distinctive molecular features. Differential analysis revealed genes that were upregulated in BPH-only and downregulated in BPH/PCa, and vice versa. Symptomatic BPH men had upregulation of T-cell activation markers (TCR, CD3, ZAP70, IL-2 and IFN-γ and chemokine receptors, CXCL9/10) expression. In contrast, men with BPH/PCa had upregulation of NKX3-1 and HOXB13 transcription factors associated with luminal epithelial progenitors but depleted of immune cells, suggesting a cell-autonomous role in immune evasion. Symptomatic BPH with immune-enriched landscapes may support anti-tumor immunity. RNA sequencing of benign prostate biopsy tissue showing upregulation of NKX3-1 and HOXB13 with the absence of T-cells might help in identifying men at higher risk of future PCa development, which may be useful in determining ongoing PCa screening.
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RATIONALE AND OBJECTIVES: To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually. Median and optimized rVFA thresholds were determined according to published methods. Kaplan Meier and log-rank tests were used to estimate OS. Multivariate models were developed to identify interactions between sex, rVFA, and OS. Unsupervised gene expression analysis of PDAC tumors from The Cancer Genome Atlas (TCGA) was performed to identify metabolic pathways with similar survival patterns to rVFA. RESULTS: Optimized preoperative rVFA threshold of 38.9% predicted significantly different OS in females with a median OS of 15 months (above threshold) vs 24 months (below threshold; p = 0.004). No significant threshold was identified in males. This female-specific significance was independent of age, stage, and presence of chronic pancreatitis (p = 0.02). Tumor gene expression analysis identified female-specific stratification from a five-gene signature of glutathione S-transferases. This was observed for PDAC as well as clear cell renal carcinoma and glioblastoma. CONCLUSION: CT-based assessments of visceral fat can predict pancreatic cancer OS in females. Glutathione S-transferase expression in tumors predicts female-specific OS in a similar fashion.
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Gordura Intra-Abdominal , Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Idoso , Glutationa/metabolismo , Fatores Sexuais , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Adulto , Idoso de 80 Anos ou mais , Taxa de SobrevidaRESUMO
INTRODUCTION: Some patients with renal cell carcinoma (RCC) present with venous tumor thrombus (VTT). The extent of the VTT is related to survival, so prompt surgical care is recommended. However, studies evaluating the natural history of VTT in patients with RCC are rare. We sought to evaluate the growth kinetics of VTT in patients with RCC using preoperative cross-sectional images. MATERIALS AND METHODS: We identified patients who underwent radical nephrectomy and venous tumor thrombectomy at our institution from 01/2009 to 02/2022. We included those with a minimum of 2 adequate preoperative imaging studies (contrast-enhanced Computerized Tomography (CT), noncontrast Magnetic resonance imaging (MRI), or contrast-enhanced MRI), at least 14 days apart. We measured VTT in each study to calculate growth rate, and evaluated predictors of faster growth (demographics, histology, laterality, tumor diameter, and staging). To assess the relation between clinical variables and VTT growth, we used the Wilcoxon Rank-Sum, Kruskal-Wallis, and Spearman correlation tests. RESULTS: A total of 30 patients were included in the analysis. The median time interval between studies was 33 days. Patients were mostly Caucasian and Males (90% and 70%, respectively). Most patients underwent a CT scan as their initial imaging study (66%), followed with an MRI as second study (73%). The mean venous tumor thrombus growth rate was 0.3 mm/d (standard deviation of 0.5mm), and only rhabdoid/sarcomatoid differentiation showed an association with tumor thrombus growth rate (0.3 vs. 0.63 mm/d, Pâ¯=â¯0.038). CONCLUSIONS: To the best of our knowledge, this is the first study evaluating the natural growth rate of venous tumor thrombus in patients with renal cell carcinoma. We found that tumor thrombi grew an average of 0.3 mm/d (1.0 cm/month) and that those with sarcomatoid and/or rhabdoid differentiation grew faster (0.63 mm/d). Further studies are needed to validate these results and provide a better understanding of tumor thrombus kinetics.
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Carcinoma de Células Renais , Neoplasias Renais , Trombose , Masculino , Humanos , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Veia Cava Inferior/patologia , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/complicações , Nefrectomia/métodos , Trombectomia/métodosRESUMO
α-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the α-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous α-particle emission distribution concentrated at bone-tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that 223Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of α-particle radiopharmaceutical therapies.
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Neoplasias Ósseas , Neoplasias da Próstata , Masculino , Humanos , Compostos Radiofarmacêuticos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Autorradiografia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundárioRESUMO
Advances in MRI technology have led to the development of low-field-strength (hereafter, "low-field") (0.55 T) MRI systems with lower weight, fewer shielding requirements, and lower cost than those of traditional (1.5-3 T) systems. The trade-offs of lower signal-to-noise ratio (SNR) at 0.55 T are partially offset by patient safety and potential comfort advantages (eg, lower specific absorption rate and a more cost-effective larger bore diameter) and physical advantages (eg, decreased T2* decay, shorter T1 relaxation times). Image reconstruction advances leveraging developing technologies (such as deep learning-based denoising) can be paired with traditional techniques (such as increasing the number of signal averages) to improve SNR. The overall image quality produced by low-field MRI systems, although perhaps somewhat inferior to 1.5-3 T MRI systems in terms of SNR, is nevertheless diagnostic for a broad variety of body imaging applications. Effective low-field body MRI requires (a) an understanding of the trade-offs resulting from lower field strengths, (b) an approach to modifying routine sequences to overcome SNR challenges, and (c) a workflow for carefully selecting appropriate patients. The authors describe the rationale, opportunities, and challenges of low-field body MRI; discuss important considerations for low-field imaging with common body MRI sequences; and delineate a variety of use cases for low-field body MRI. The authors also include lessons learned from their preliminary experience with a new low-field MRI system at a tertiary care center. Finally, they explore the future of low-field MRI, summarizing current limitations and potential future developments that may enhance the clinical adoption of this technology. ©RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center. See the invited commentary by Venkatesh in this issue.
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Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Razão Sinal-Ruído , Segurança do PacienteRESUMO
The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions regarding the workup of patients with prostate cancer, risk stratification and management of localized disease, post-treatment monitoring, and treatment of recurrence and advanced disease. The Guidelines sections included in this article focus on the management of metastatic castration-sensitive disease, nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). Androgen deprivation therapy (ADT) with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer. For patients with nonmetastatic CRPC, ADT is continued with or without the addition of certain secondary hormone therapies depending on prostate-specific antigen doubling time. In the mCRPC setting, ADT is continued with the sequential addition of certain secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, the presence or absence of visceral disease, symptoms, and potential side effects.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Hormônios/uso terapêutico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/terapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológicoRESUMO
Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of obesity, MRI-determined abdominal adipose tissue volumes, and insulin resistance with PET-determined amyloid and tau uptake in default mode network areas, and MRI-determined brain volume and cortical thickness in AD cortical signature in the cognitively normal midlife population. Thirty-two middle-aged (age: 51.27±6.12 years, 15 males, body mass index (BMI): 32.28±6.39 kg/m2) cognitively normal participants, underwent bloodwork, brain and abdominal MRI, and amyloid and tau PET scan. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi-automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer was used to automatically segment brain regions using a probabilistic atlas. PET scans were acquired using [11C]PiB and AV-1451 tracers and were analyzed using PET unified pipeline. The association of brain volumes, cortical thicknesses, and PiB and AV-1451 standardized uptake value ratios (SUVRs) with BMI, VAT/SAT ratio, and insulin resistance were assessed using Spearman's partial correlation. VAT/SAT ratio was associated significantly with PiB SUVRs in the right precuneus cortex (p=0.034) overall, controlling for sex. This association was significant only in males (p=0.044), not females (p=0.166). Higher VAT/SAT ratio and PiB SUVRs in the right precuneus cortex were associated with lower cortical thickness in AD-signature areas predominantly including bilateral temporal cortices, parahippocampal, medial orbitofrontal, and cingulate cortices, with age and sex as covariates. Also, higher BMI and insulin resistance were associated with lower cortical thickness in bilateral temporal poles. In midlife cognitively normal adults, we demonstrated higher amyloid pathology in the right precuneus cortex in individuals with a higher VAT/SAT ratio, a marker of visceral obesity, along with a lower cortical thickness in AD-signature areas associated with higher visceral obesity, insulin resistance, and amyloid pathology.
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Purpose To analyze the frequency of discrepant interpretations of progressive disease (PD) between routine clinical and formal Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 interpretations in patients enrolled in solid tumor clinical trials and investigate the causes of discordance. Materials and Methods This retrospective study included patients in solid tumor clinical trials undergoing imaging response assessments based on RECIST 1.1 from January to July 2021. Routine clinical interpretations (RCIs) performed as part of standard workflow and not requiring formal use of any established response criteria were compared with separate local core laboratory interpretations (CLIs) by specially trained radiologists who used software that tracks target lesion measurements, changes in nontarget lesions, and appearance of new lesions longitudinally. The comparison focused on discordant interpretations of PD. Results Among 1053 patients who had both RCIs and CLIs performed, PD was diagnosed on one or both reads in 327 patients (median age, 63.6 [range, 22.4-83.2] years; 57.8% female patients). The RCIs and CLIs agreed with PD status in 65% (213 of 327) of assessments. In 32% (105 of 327) of assessments, RCIs overdiagnosed PD when CLIs diagnosed stable disease, and in 3% (nine of 327), CLIs diagnosed PD when RCIs diagnosed stable disease. Reasons for discrepant RCIs of PD included erroneous target lesion measurements (58%, 61 of 105), erroneous diagnosis of nontarget progression (30%, 32 of 105), and misclassification of new lesions as cancer (11%, 12 of 105). Most patients (93%, 98 of 105) with RCI overdiagnosis of PD remained in the clinical trial for one or more treatment cycles. Conclusion PD was frequently overdiagnosed on RCIs versus formal RECIST 1.1 CLIs which could result in patients removed from the clinical trial inappropriately. Keywords: Oncology, Cancer, Tumor Response, MR Imaging, CT © RSNA, 2023 See also commentary by Margolis and Ruchalski in this issue.
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Neoplasias , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Neoplasias/diagnóstico por imagem , Neoplasias/terapiaRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC's excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear. METHODS: We performed a phase 1b observational study (ClinicalTrials.gov ID NCT04542291; registered 09/09/2020) to test the safety and tolerability of dapagliflozin (5 mg p.o./day × 2 weeks escalated to 10 mg p.o./day × 6 weeks) added to standard Gemcitabine and nab-Paclitaxel (GnP) chemotherapy in patients with locally advanced and/or metastatic PDAC. Markers of efficacy including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) response, CT-based volumetric body composition measurements, and plasma chemistries for measuring metabolism and tumor burden were also analyzed. RESULTS: Of 23 patients who were screened, 15 enrolled. One expired (due to complications from underlying disease), 2 dropped out (did not tolerate GnP chemotherapy) during the first 4 weeks, and 12 completed. There were no unexpected or serious adverse events with dapagliflozin. One patient was told to discontinue dapagliflozin after 6 weeks due to elevated ketones, although there were no clinical signs of ketoacidosis. Dapagliflozin compliance was 99.4%. Plasma glucagon increased significantly. Although abdominal muscle and fat volumes decreased; increased muscle-to-fat ratio correlated with better therapeutic response. After 8 weeks of treatment in the study, partial response (PR) to therapy was seen in 2 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. After dapagliflozin discontinuation (and chemotherapy continuation), an additional 7 patients developed the progressive disease in the subsequent scans measured by increased lesion size as well as the development of new lesions. Quantitative imaging assessment was supported by plasma CA19-9 tumor marker measurements. CONCLUSIONS: Dapagliflozin is well-tolerated and was associated with high compliance in patients with advanced, inoperable PDAC. Overall favorable changes in tumor response and plasma biomarkers suggest it may have efficacy against PDAC, warranting further investigation.
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BACKGROUND: Obesity is a known risk factor for developing endometrial cancer. However, the association of obesity with endometrial cancer (EC) outcomes has not been clearly established. This study examined how outcomes in women with early stage EC vary with body composition measured via computed tomography (CT). METHODS: In this retrospective study, patients diagnosed with EC international Federation of Gynecology and Obstetrics stages I-III and available CT scans were included. Automatica software was used to assess the areas of visceral adipose tissue, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) and skeletal muscle area. RESULTS: Of 293 patient charts assessed, 199 met eligibility criteria. Median body mass index (BMI) was 32.8 kg/m2 (interquartile range [IQ] = 26.8-38.9); 61.8% had histologic subtype endometrioid carcinoma. Adjusted for age, international Federation of Gynecology and Obstetrics stage, and histologic subtype, a BMI of at least 30 vs less than 30 kg/m2 was associated with lower endometrial cancer-specific survival (ECSS) (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.27 to 4.25) and overall survival (OS) (HR = 2.7, 95% CI = 1.35 to 5.39). Higher IMAT 75th vs 25th percentile and SAT of at least 225.6 vs less than 225.6 cm2 were associated with lower ECSS (HR = 1.53, 95% CI = 1.1 to 2.13, and HR = 2.57, 95% CI = 1.13 to 5.88) and OS (HR = 1.50, 95% CI = 1.11 to 2.02, and HR = 2.46, 95% CI = 1.2 to 5.01), respectively. The association of visceral adipose tissue (75th vs 25th percentile) with ECSS and OS was not statistically significant (HR = 1.42, 95% CI = 0.91 to 2.22, and HR = 1.24, 95% CI = 0.81 to 1.89). CONCLUSION: Higher BMI, IMAT, and SAT were associated with higher mortality from EC and lower OS. A better understanding of the mechanisms underlying these relationships could inform strategies to improve patient outcomes.
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Carcinoma Endometrioide , Neoplasias do Endométrio , Humanos , Feminino , Estudos Retrospectivos , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Carcinoma Endometrioide/patologia , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/epidemiologia , Composição CorporalRESUMO
Obesity is a chronic, relapsing, progressive disease of excess adiposity that increases the risk of developing at least 13 types of cancer. This report provides a concise review of the current state of the science regarding metabolic and bariatric surgery and obesity pharmacotherapy related to cancer risk. Meta-analyses of cohort studies report that metabolic and bariatric surgery is independently associated with a lower risk of incident cancer than nonsurgical obesity care. Less is known regarding the cancer-preventive effects of obesity pharmacotherapy. The recent approval and promising pipeline of obesity drugs will provide the opportunity to understand the potential for obesity therapy to emerge as an evidence-based cancer prevention strategy. There are myriad research opportunities to advance our understanding of how metabolic and bariatric surgery and obesity pharmacotherapy may be used for cancer prevention.
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Cirurgia Bariátrica , Neoplasias , Humanos , Adiposidade , Cirurgia Bariátrica/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/etiologia , Neoplasias/prevenção & controle , Obesidade/complicações , Obesidade/cirurgia , RiscoRESUMO
Body composition assessment (ie, the measurement of muscle and adiposity) impacts several cancer-related outcomes including treatment-related toxicities, treatment responses, complications, and prognosis. Traditional modalities for body composition measurement include body mass index, body circumference, skinfold thickness, and bioelectrical impedance analysis; advanced imaging modalities include dual energy x-ray absorptiometry, computerized tomography, magnetic resonance imaging, and positron emission tomography. Each modality has its advantages and disadvantages, thus requiring an individualized approach in identifying the most appropriate measure for specific clinical or research situations. Advancements in imaging approaches have led to an abundance of available data, however, the lack of standardized thresholds for classification of abnormal muscle mass or adiposity has been a barrier to adopting these measurements widely in research and clinical care. In this review, we discuss the different modalities in detail and provide guidance on their unique opportunities and challenges.
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Composição Corporal , Neoplasias , Humanos , Neoplasias/diagnóstico por imagem , Índice de Massa Corporal , Dobras Cutâneas , Impedância Elétrica , Absorciometria de Fóton , Tomógrafos Computadorizados , Imageamento por Ressonância Magnética , Tomografia por Emissão de PósitronsRESUMO
Aims: Targeting tumor metabolism may improve the outcomes for patients with glioblastoma (GBM). To further preclinical efforts targeting metabolism in GBM, we tested the hypothesis that brain tumors can be stratified into distinct metabolic groups with different patient outcomes. Therefore, to determine if tumor metabolites relate to patient survival, we profiled the metabolomes of human gliomas and correlated metabolic information with clinical data. Results: We found that isocitrate dehydrogenase-wildtype (IDHwt) GBMs are metabolically distinguishable from IDH mutated (IDHmut) astrocytomas and oligodendrogliomas. Survival of patients with IDHmut gliomas was expectedly more favorable than those with IDHwt GBM, and metabolic signatures can stratify IDHwt GBMs subtypes with varying prognoses. Patients whose GBMs were enriched in amino acids had improved survival, while those whose tumors were enriched for nucleotides, redox molecules, and lipid metabolites fared more poorly. These findings were recapitulated in validation cohorts using both metabolomic and transcriptomic data. Innovation: Our results suggest the existence of metabolic subtypes of GBM with differing prognoses, and further support the concept that metabolism may drive the aggressiveness of human gliomas. Conclusions: Our data show that metabolic signatures of human gliomas can inform patient survival. These findings may be used clinically to tailor novel metabolically targeted agents for GBM patients with different metabolic phenotypes. Antioxid. Redox Signal. 39, 942-956.
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Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Mutação , Glioma/genética , Glioma/metabolismo , Astrocitoma/genética , Astrocitoma/metabolismo , Astrocitoma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismoRESUMO
The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, recurrent, and metastatic disease. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. These NCCN Guidelines Insights summarizes much of the panel's discussions for the 4.2022 and 1.2023 updates to the guidelines regarding systemic therapy for metastatic prostate cancer.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Medição de RiscoRESUMO
Lung cancer is the leading cause of cancer-related death. Intriguingly, males with non-small cell lung cancer (NSCLC) have a higher mortality rate than females. Here, we investigated the role of serine metabolism as a predictive marker for sensitivity to the antifolate pemetrexed in male and female NSCLC cell lines. Using [13C6] glucose tracing in NSCLC cell lines, we found that a subset of male cells generated significantly more serine from glucose than female cells. Higher serine biosynthesis was further correlated with increased sensitivity to pemetrexed in male cells only. Concordant sex differences in metabolic gene expression were evident in NSCLC and pan-cancer transcriptome datasets, suggesting a potential mechanism with wide-reaching applicability. These data were further validated by integrating antifolate drug cytotoxicity and metabolic pathway transcriptome data from pan-cancer cell lines. Together, these findings highlight the importance of considering sex differences in cancer metabolism to improve treatment for all patients.