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BACKGROUND: There remains a paucity of data regarding the efficacy of immune checkpoint therapy (ICT) combinations ± vascular endothelial growth factor (VEGF) targeted therapy (TT) in translocation renal cell carcinoma (tRCC). METHODS: This is a retrospective study of patients with advanced tRCC treated with ICT combinations at 11 centers in the US, France, and Belgium. Only cases with confirmed fluorescence in situ hybridization (FISH) were included. Objective response rates (ORR) and progression-free survival (PFS) were assessed by RECIST, and overall survival (OS) was estimated by Kaplan-Meier methods. RESULTS: There were 29 patients identified with median age of 38 (21-70) years, and F:M ratio 0.9:1. FISH revealed TFE3 and TFEB translocations in 22 and 7 patients, respectively. Dual ICT and ICT + VEGF TT were used in 18 and 11 patients, respectively. Seventeen (59%) patients received ICT combinations as first-line therapy. ORR was 1/18 (5.5%) for dual ICT and 4/11 (36%) for ICT + VEGF TT. At a median follow-up of 12.9 months, median PFS was 2.8 and 5.4 months in the dual ICT and ICT + VEGF TT groups, respectively. Median OS from metastatic disease was 17.8 and 30.7 months in the dual ICT and ICT + VEGF TT groups, respectively. CONCLUSION: In this retrospective study of advanced tRCC, limited response and survival were seen after frontline dual ICT combination therapy, while ICT + VEGF TT therapy offered some efficacy. Due to the heterogeneity of tRCC, insights into the biological underpinnings are necessary to develop more effective therapies.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Estudos Retrospectivos , Hibridização in Situ FluorescenteRESUMO
BACKGROUND: Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated. PATIENTS AND METHODS: Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (Sâ +â R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGFR TT, and inclusion of cabozantinib in the post-ICT TT regimen. RESULTS: 29/57 patients had S dedifferentiation and 19 had R dedifferentiation. The most frequently used TT was cabozantinib (43.9%) followed by selective VEGFR TT (22.8%). The median time on TT was 6.4 months for all, 6.1 months for those with S dedifferentiation, 15.6 months for R dedifferentiation, and 6.1 months for Sâ +â R dedifferentiation. Median OS from initiation of TT was 24.9 months for the entire cohort, and the ORR was 20.0%. Patients with R dedifferentiation had significantly longer time on TT than those with S dedifferentiation (HR 0.44, 95% CI, 0.21-0.94). IMDC risk was associated with OS. CONCLUSIONS: A subset of patients with S/R dedifferentiation derive clinical benefit from TT after they have progressive disease on ICT. Patients with R dedifferentiation appeared to derive more benefit from TT than those with S dedifferentiation.
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In clinical diagnostics and research involving histopathology, formalin-fixed paraffin-embedded (FFPE) tissue is almost universally favored for its superb image quality. However, tissue processing time (>24 h) can slow decision-making. In contrast, fresh frozen (FF) processing (<1 h) can yield rapid information but diagnostic accuracy is suboptimal due to lack of clearing, morphologic deformation and more frequent artifacts. Here, we bridge this gap using artificial intelligence. We synthesize FFPE-like images ("virtual FFPE") from FF images using a generative adversarial network (GAN) from 98 paired kidney samples derived from 40 patients. Five board-certified pathologists evaluated the results in a blinded test. Image quality of the virtual FFPE data was assessed to be high and showed a close resemblance to real FFPE images. Clinical assessments of disease on the virtual FFPE images showed a higher inter-observer agreement compared to FF images. The nearly instantaneously generated virtual FFPE images can not only reduce time to information but can facilitate more precise diagnosis from routine FF images without extraneous costs and effort.
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Formaldeído , Perfilação da Expressão Gênica , Inteligência Artificial , Perfilação da Expressão Gênica/métodos , Humanos , Inclusão em Parafina/métodos , Fixação de Tecidos/métodosRESUMO
Profiling of both the genome and the transcriptome promises a comprehensive, functional readout of a tissue sample, yet analytical approaches are required to translate the increased data dimensionality, heterogeneity and complexity into patient benefits. We developed a statistical approach called Texomer ( https://github.com/KChen-lab/Texomer ) that performs allele-specific, tumor-deconvoluted transcriptome-exome integration of autologous bulk whole-exome and transcriptome sequencing data. Texomer results in substantially improved accuracy in sample categorization and functional variant prioritization.
Assuntos
Perfilação da Expressão Gênica/métodos , Genoma Humano , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias/genética , Transcriptoma/genética , Alelos , DNA de Neoplasias/genética , Exoma/genética , Humanos , Mutação , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The role of radiotherapy in metastatic renal cell carcinoma is controversial. We prospectively tested the feasibility and efficacy of radiotherapy to defer systemic therapy for patients with oligometastatic renal cell carcinoma. METHODS: This single-arm, phase 2, feasibility trial was done at one centre in the USA (The MD Anderson Cancer Center, Houston, TX, USA). Patients (aged ≥18 years) with five or fewer metastatic lesions, an Eastern Cooperative Oncology Group status of 0-2, and no more than one previous systemic therapy (if this therapy was stopped at least 1 month before enrolment) without limitations on renal cell carcinoma histology were eligible for inclusion. Patients were treated with stereotactic body radiotherapy (defined as ≤5 fractions with ≥7 Gy per fraction) to all lesions and maintained off systemic therapy. When lesion location precluded safe stereotactic body radiotherapy, patients were treated with hypofractionated intensity-modulated radiotherapy regimes consisting of 60-70 Gy in ten fractions or 52·5-67·5 Gy in 15 fractions. Additional rounds of radiotherapy were allowed to treat subsequent sites of progression. Co-primary endpoints were feasibility (defined as all planned radiotherapy completed with <7 days unplanned breaks) and progression-free survival. All efficacy analyses were intention-to-treat. Safety was analysed in the as-treated population. A second cohort, with the aim of assessing the feasibility of sequential stereotactic body radiotherapy alone in patients with low-volume metastatic disease, was initiated and will be reported separately. This study is registered with ClinicalTrials.gov, NCT03575611. FINDINGS: 30 patients (six [20%] women) were enrolled from July 13, 2018, to Sept 18, 2020. All patients had clear cell histology and had a nephrectomy before enrolment. All patients completed at least one round of radiotherapy with less than 7 days of unplanned breaks. At a median follow-up of 17·5 months (IQR 13·2-24·6), median progression-free survival was 22·7 months (95% CI 10·4-not reached; 1-year progression-free survival 64% [95% CI 48-85]). Three (10%) patients had severe adverse events: two grade 3 (back pain and muscle weakness) and one grade 4 (hyperglycaemia) adverse events were observed. There were no treatment-related deaths. INTERPRETATION: Sequential radiotherapy might facilitate deferral of systemic therapy initiation and could allow sustained systemic therapy breaks for select patients with oligometastatic renal cell carcinoma. FUNDING: Anna Fuller Foundation, the Cancer Prevention and Research Institute of Texas (CPRIT), and the National Cancer Institute.
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Carcinoma de Células Renais/radioterapia , Neoplasias Renais/radioterapia , Radioterapia de Intensidade Modulada/mortalidade , Idoso , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/patologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Texas/epidemiologiaRESUMO
Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney represents a poorly understood clinicopathologic entity with pathologic features that overlap between benign renal oncocytoma (RO) and malignant chromophobe renal cell carcinoma (ChRCC). Consequently, characterization of HOCT and its separation from the foregoing entities are clinically important. The aim of this study was to describe the pathologic and molecular features of HOCT and to compare them with those of RO and ChRCC. We retrospectively identified a cohort of 73 cases with renal oncocytic tumors (19 RO, 27 HOCT, and 27 ChRCC) for whom clinical follow-up data were available by 2 tertiary care hospitals. All cases were sporadic except for 2 HOCTs that were associated with Birt-Hogg-Dubé syndrome. Lesional tissues were retrieved for molecular analysis. We performed targeted gene sequencing of all exons of 261 cancer related genes on a subset of HOCT samples (n = 16). Gene expression profiling of a customized codeset was conducted on 19 RO, 24 HOCT, and 27 ChRCC samples. Clinicopathologic characteristics as well as DNA copy number alterations, mutational and transcriptional features of HOCT derived from sequencing and expression profiling data are described and compared to those in RO and ChRCC. HOCTs were more frequently multifocal and did not exhibit mutations in genes that are recurrently mutated in RO or ChRCC but showed copy number alterations primarily involving losses in chromosomes 1 and X/Y. The mRNA transcript data show that HOCT can be separated from RO and ChRCC. Hence, HOCT appears to represent a distinct renal tumor entity with genomic features that are intermediate between those of RO and ChRCC.
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Adenoma Oxífilo/genética , Adenoma Oxífilo/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , TranscriptomaRESUMO
Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.
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Guias de Prática Clínica como Assunto/normas , Neoplasias Testiculares/classificação , Neoplasias Testiculares/terapia , Terapia Combinada , Humanos , Masculino , Metástase Neoplásica , Prognóstico , Neoplasias Testiculares/diagnósticoRESUMO
BACKGROUND: Adrenocortical carcinoma (ACC) has a poor prognosis and there is an unmet clinical need for biomarkers to improve both diagnostic and prognostic assessment. Pituitary-tumor transforming gene (PTTG1) has been shown to modulate cancer invasiveness and response to therapy. The potential role of PTTG1 protein levels in ACC has not been previously addressed. We assessed whether increased nuclear protein expression of PTTG1 distinguished ACCs from adrenocortical adenomas (ACAs). METHODS: Patients with ACC or ACA were identified from prospective tissue banks at two independent institutions. Two tissue microarrays (TMAs) consisting of adrenal specimens from 131 patients were constructed and clinically annotated. Immunohistochemical analysis for PTTG1 and Ki-67 was performed on each TMA. RESULTS: TMA-1 (n = 80) contained 20 normal adrenals, 20 ACAs, and 40 ACCs, and the validation, TMA-2 (n = 51), consisted of 10 normal adrenals, 14 ACAs, and 27 ACCs. On TMA-1, nuclear staining of PTTG1 was detected in 12 (31%) ACC specimens, while all ACAs and normal adrenal glands were negative for PTTG1. On TMA-2, 20 (74%) of the ACC tumors demonstrated PTTG1 nuclear staining of PTTG1, and 13 (93%) ACA and 4 (44%) normal adrenal glands were negative for PTTG1. ACC tumors with increased PTTG1 protein staining had a significantly higher Ki-67 index (p < 0.001) than those with lower levels of PTTG1. CONCLUSIONS: Increased nuclear protein expression of PTTG1 was observed in malignant adrenal tumors. PTTG1 correlated with Ki-67 in two independent TMAs. PTTG1 is a promising biologic marker in the evaluation of adrenal tumors.
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Neoplasias do Córtex Suprarrenal/diagnóstico , Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/diagnóstico , Biomarcadores Tumorais/metabolismo , Securina/metabolismo , Neoplasias do Córtex Suprarrenal/metabolismo , Glândulas Suprarrenais/metabolismo , Adenoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis in some cancers. However, the expression and biological role of T-UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of Uc.416 + A and analyze the association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC. METHODS: Expression of Uc.416 + A in 35 RCC tissues, corresponding normal kidney tissues and 13 types of normal tissue samples was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We performed a cell growth and migration assay in RCC cell line 786-O transfected with negative control and siRNA for Uc.416 + A. We evaluated the relation between Uc.416 + A and miR-153, which has a complimentary site of Uc.416 + A. RESULTS: qRT-PCR analysis revealed that the expression of Uc.416 + A was higher in RCC tissues than that in corresponding normal kidney tissues. Inhibition of Uc.416 + A reduced cell growth and cell migration activity. There was an inverse correlation between Uc.416 + A and miR-153. Western blot analysis showed Uc.416 + A modulated E-cadherin, vimentin and snail. The expression of Uc.416 + A was positively associated with the expression of SNAI1, VIM and inversely associated with the expression of CDH1. CONCLUSIONS: The expression of Uc.416 + A was upregulated in RCC and especially in RCC tissues with sarcomatoid change. Uc.416 + A promoted epithelial-to-mesenchymal transition through miR-153. These results suggest that Uc.416 + A may be a promising therapeutic target.
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Carcinoma de Células Renais/metabolismo , Transição Epitelial-Mesenquimal/genética , Neoplasias Renais/metabolismo , MicroRNAs/fisiologia , RNA não Traduzido/metabolismo , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , RNA não Traduzido/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: The immune profile of sarcomatoid renal cell carcinoma (sRCC), including the programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) status, has not been well characterized. METHODS: An immunohistochemical digital analysis of PD-L1, PD-1, CD4, and CD8 was performed on nephrectomy specimens from 118 sRCC patients and 92 nonsarcomatoid clear cell renal cell carcinoma (ccRCC) patients. The clinical characteristics of the population were compared between sRCC and ccRCC. Overall survival was estimated, and comparisons were made between PD-L1-positive and PD-L1-negative groups as well as tumor-infiltrating lymphocyte (TIL)-high and TIL-low groups. RESULTS: The PD-L1 H-score of sRCC (mean, 3.7; range, 0-192.1) was significantly higher than the score of grade 4 ccRCC (P = .001), and 41.3% of sRCC cases showed a PD-L1 H-score ≥ 10. The PD-1-positive cell density was significantly higher in sRCC versus ccRCC within the tumor and at the invasive front. The intratumoral CD8-positive cell density was significantly higher in sRCC versus ccRCC. Forty-one percent in the sarcomatoid component of sRCC and 8% in the epithelioid component of sRCC had an adaptive immune resistance phenotype (PD-L1-positive and TIL-positive), whereas only 1% in ccRCC had the type I phenotype. CONCLUSIONS: sRCC showed higher PD-L1 expression and higher PD-1- and CD8-positive cell density than grade 4 ccRCC. The results indicate a notable immunosuppressive environment in sRCC. Despite advances in the treatment of advanced-stage renal cell carcinoma, sRCC still has a poor prognosis. This work describes highly immunosuppressive characteristics of sRCC in comparison with an appropriate ccRCC control. The results suggest PD-1/PD-L1 blockade therapy as a potential therapeutic approach for sRCC. Cancer 2017;123:4823-31. © 2017 American Cancer Society.
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Antígeno B7-H1/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Sarcoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Diferenciação Celular/imunologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Análise de SobrevidaRESUMO
PURPOSE: We studied overall survival and prognostic factors in patients with sarcomatoid renal cell carcinoma treated with nephrectomy and systemic therapy in the cytokine and targeted therapy eras. MATERIALS AND METHODS: This is a retrospective study of patients with sarcomatoid renal cell carcinoma who underwent nephrectomy and received systemic therapy at our center in the cytokine era (1987 to 2005) or the targeted therapy era (2006 to 2015). Multivariate regression models were used to determine the association of covariables with survival. RESULTS: Of the 199 patients with sarcomatoid renal cell carcinoma 167 (83.9%) died (median overall survival 16.5 months, 95% CI 15.2-20.9). Survival of patients with clear cell histology was significantly longer vs those with nonclear cell histology (p = 0.034). Patients with synchronous metastatic disease had significantly shorter survival than patients with metachronous metastatic disease (median 12.1 vs 23.3 months, p = 0.0064). Biopsy of the primary tumor or a metastatic site could detect the presence of sarcomatoid features in only 7.5% of cases. Although a significant improvement in survival rate was observed in the first year in patients treated in the targeted therapy era (p = 0.011), this effect was attenuated at year 2, disappeared at years 3 to 5 after diagnosis and was not evident in patients with poor risk features. CONCLUSIONS: Patients with sarcomatoid renal cell carcinoma still have poor prognosis with no clear long-term benefit of targeted therapy. This underscores the need to develop more effective systemic therapies for these patients.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Nefrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/secundário , Terapia Combinada , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS). PATIENTS AND METHODS: RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000-2015 at eight academic institutions in North America and France. The Kaplan-Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS. RESULTS: In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9-48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months. CONCLUSIONS: RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.
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Carcinoma Medular , Neoplasias Renais , Adolescente , Adulto , Carcinoma Medular/tratamento farmacológico , Carcinoma Medular/epidemiologia , Carcinoma Medular/mortalidade , Carcinoma Medular/cirurgia , Criança , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/epidemiologia , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Management of metastatic renal cell carcinoma with sarcomatoid dedifferentiation remains a therapeutic challenge with no standard treatment strategies. We evaluated whether metastasectomy has any survival benefit in patients with metastatic sarcomatoid dedifferentiation treated with radical nephrectomy. MATERIALS AND METHODS: From an institutional database of 273 patients with sarcomatoid dedifferentiation treated with nephrectomy we matched 80 with synchronous and asynchronous metastases for age, ECOG (Eastern Cooperative Oncology Group) performance status, histology and lymph node status. Matched pairs were then retained only if patients who did not undergo metastasectomy were alive at metastasectomy comparable to matched surgical patients to decrease the bias of survival outcomes. Overall survival from nephrectomy was studied using univariable and multivariable proportional hazards regression. RESULTS: Median overall survival was 8.3 (95% CI 6.5-10.5) and 18.5 months (95% CI 11.5-42.9) in patients with synchronous and asynchronous metastases, respectively. Overall survival in patients who underwent metastasectomy for synchronous metastasis compared to nonsurgical patients was 8.4 and 8.0 months (p = 0.35), respectively. Similarly, overall survival in patients with asynchronous metastases treated with metastasectomy compared to the nonsurgical group was 36.2 and 13.7 months, respectively (p = 0.29). On multivariable analysis positive lymph nodes at nephrectomy were associated with an increased risk of death in the synchronous and asynchronous patient subgroups (HR 2.1, 95% CI 1.1-4.0, p = 0.03 and HR 3.3, 95% CI 1.2-9.2, p = 0.02, respectively). CONCLUSIONS: In the current study there was no clear evidence of benefit in patients with sarcomatoid dedifferentiation who underwent metastasectomy after nephrectomy. Particularly, the group of patients with pathological lymph node positive disease at nephrectomy had considerably worse survival.
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Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Metastasectomia/métodos , Sarcoma/cirurgia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/secundário , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Masculino , Nefrectomia , Estudos Retrospectivos , Sarcoma/diagnóstico , Sarcoma/secundário , Taxa de Sobrevida/tendências , Texas/epidemiologiaRESUMO
OBJECTIVES: To identify the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) treated with either pazopanib or sunitinib and assess whether PM is an independent prognostic variable in the current therapeutic environment. PATIENTS AND METHODS: A retrospective review of patients with mRCC in an outpatient clinic was carried out for the period January 2006 to November 2011. Patient characteristics, including demographics, laboratory data and outcomes, were analysed. Baseline characteristics were compared using chi-squared and t-tests and overall survival (OS) and cancer-specific survival (CSS) rates were estimated using Kaplan-Meier methods. Predictors of OS were analysed using Cox regression. RESULTS: A total of 228 patients were reviewed, of whom 44 (19.3%) had PM and 184 (81.7%) had metastases to sites other than the pancreas. The distribution of baseline characteristics was equal in both groups, with the exception of a higher incidence of previous nephrectomy, diabetes and number of metastatic sites in the PM group. Four patients had isolated PM, but the majority of patients (68%) with PM had at least three different organ sites of metastases, as compared with 29% in patients without PM (P < 0.01). The distribution of organ sites of metastases was similar, excluding the pancreas, in those with and those without PM (P > 0.05). The median OS was 39 months (95% confidence interval [CI] 24-57, hazard ratio 0.66, 95% CI 0.42-0.94; P = 0.02) for patients with PM, compared with 26 months (95% CI 21-31) for patients without PM (P < 0.01). CSS was 42 months (95% CI 30-57) in the PM group and 27 months (95% CI 22-33) in the control group (P = 0.05). CONCLUSIONS: Despite a higher number of affected organ sites in the PM cohort, mRCC behaviour in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumour features associated with PM may represent a less aggressive tumour phenotype.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/secundário , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Pancreáticas/secundário , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Indazóis , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sunitinibe , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Rhabdoid histology in clear-cell renal cell carcinoma is associated with a poor prognosis. The prognosis of patients with clear-cell renal cell carcinoma may also be influenced by molecular alterations. The aim of this study was to evaluate the association between histologic features and salient molecular changes in rhabdoid clear-cell renal cell carcinoma. We macrodissected the rhabdoid and clear-cell epithelioid components from 12 cases of rhabdoid clear-cell renal cell carcinoma. We assessed cancer-related mutations from eight cases using a clinical next-generation exome-sequencing platform. The transcriptome of rhabdoid clear-cell renal cell carcinoma (n=8) and non-rhabdoid clear-cell renal cell carcinoma (n=37) was assessed by RNA-seq and gene expression microarray. VHL (63%) showed identical mutations in all regions from the same tumor. BAP1 (38%) and PBRM1 (13%) mutations were identified in the rhabdoid but not in the epithelioid component and were mutually exclusive in 3/3 cases and 1 case, respectively. SETD2 (63%) mutations were discordant between different histologic regions in 2/5 cases, with mutations called only in the epithelioid and rhabdoid components, respectively. The transcriptome of rhabdoid clear-cell renal cell carcinoma was distinct from advanced-stage and high-grade clear-cell renal cell carcinoma. The diverse histologic components of rhabdoid clear-cell renal cell carcinoma, however, showed a similar transcriptomic program, including a similar prognostic gene expression signature. Rhabdoid clear-cell renal cell carcinoma is transcriptomically distinct and shows a high rate of SETD2 and BAP1 mutations and a low rate of PBRM1 mutations. Driver mutations in clear-cell renal cell carcinoma are often discordant across different morphologic regions, whereas the gene expression program is relatively stable. Molecular profiling of clear-cell renal cell carcinoma may improve by assessing for gene expression and sampling tumor foci from different histologic regions.
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Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Medicina de Precisão , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Microdissecção e Captura a Laser , Análise de Sequência com Séries de Oligonucleotídeos , TranscriptomaRESUMO
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These NCCN Guidelines Insights highlight the recent updates/changes in these guidelines, and updates include axitinib as first-line treatment option for patients with clear cell renal carcinoma, new data to support pazopanib as subsequent therapy for patients with clear cell carcinoma after first-line treatment with another tyrosine kinase inhibitor, and guidelines for follow-up of patients with renal cell carcinoma.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Axitinibe , Carcinoma de Células Renais/diagnóstico , Humanos , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Neoplasias Renais/diagnóstico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêuticoRESUMO
Germ cell tumors (GCTs) account for 95% of testicular cancers. Testicular GCTs constitute the most common solid tumor in men between the ages of 20 and 34 years, and the incidence of testicular GCTs has been increasing in the past 2 decades. Testicular GCTs are classified into 2 broad groups--pure seminoma and nonseminoma--which are treated differently. Pure seminomas, unlike nonseminomas, are more likely to be localized to the testis at presentation. Nonseminoma is the more clinically aggressive tumor associated with elevated serum concentrations of alphafetoprotein (AFP). The diagnosis of a seminoma is restricted to pure seminoma histology and a normal serum concentration of AFP. When both seminoma and elements of a nonseminoma are present, management follows that for a nonseminoma. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Testicular Cancer outline the diagnosis, workup, risk assessment, treatment, and follow-up schedules for patients with both pure seminoma and nonseminoma.
Assuntos
Seminoma/terapia , Neoplasias Testiculares/terapia , Terapia Combinada , Gerenciamento Clínico , Humanos , Masculino , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Seminoma/diagnóstico , Neoplasias Testiculares/diagnósticoRESUMO
These NCCN Guidelines Insights highlight treatment recommendations and updates specific to the management of patients with advanced non-clear cell carcinoma included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Humanos , Neoplasias Renais/diagnóstico , Terapia de Alvo MolecularRESUMO
OBJECTIVE: To describe and compare the clinical, biochemical, radiologic, and pathologic features of adrenal pheochromocytoma-ganglioneuroma (PC-GN) composites with the features of isolated pheochromocytomas (PCs) and adrenal ganglioneuromas (AGNs). METHODS: We reviewed data for PC-GN composite cases seen at a single tertiary center between 1993 and 2012 and compared them with cases of isolated AGN and relatively similar median-size PCs. RESULTS: Nine PC-GN composites were included. The median age at diagnosis was 52 years (range, 28 to 83 years) for PC-GN compared with 55 years (range, 24 to 78 years) for PC patients and 40 years (range, 18 to 64 years) for AGN patients. Similar to PCs, all PC-GN composites were associated with catecholamine overproduction, whereas AGNs were nonfunctioning. On pathology, the median tumor sizes were 7 cm (range, 2.5 to 13 cm) for PC-GN tumors, 6.5 cm (range, 3.5 to 7 cm) for PCs, and 8 cm (range, 3.2 to 20 cm) for AGNs. On computed tomography (CT) imaging, PC-GN composites and PCs were heterogeneous, with both having significantly higher postcontrast density values than AGNs, which typically looked homogeneous and had a progressive enhancement pattern without contrast washout in most cases. CONCLUSION: The presence of a PC component significantly increases tumor heterogeneity and postcontrast density values. CT imaging could be very helpful in distinguishing AGNs from both PC-GN and PC tumors, but only pathologic examination can yield the diagnosis. Clinically and radiologically, PC-GN composites are indistinguishable from PCs and need to be managed similarly.