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1.
ACG Case Rep J ; 11(5): e01352, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38706450

RESUMO

Metastasis of renal cell carcinoma (RCC) to the gastrointestinal (GI) tract is exceedingly rare. We present a case of a man in his 40s with a history of RCC that had metastasized to his abdominal wall and brain who then presented with abdominal pain and melena. On presentation, imaging showed new bone metastases and a colonic mass in the ascending colon. The biopsy of the mass from colonoscopy demonstrated RCC primary. Although rare, this case report highlights the importance of a thorough evaluation of patients with a history of RCC and considers GI tract involvement in those presenting with GI bleeding.

2.
Cancer Med ; 12(11): 12874-12880, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37212484

RESUMO

BACKGROUND: Undiagnosed Type 2 diabetes (T2D) has been associated with advanced stage cancer at diagnosis, higher mortality, and lower long-term all-cause survival. This was a RCT pilot study to examine the feasibility of a nurse-led T2D intervention for adults with newly diagnosed cancer (≤3 months), and T2D, undiagnosed or untreated with medication, conducted at an outpatient oncology clinic affiliated with a large academic institution. METHODS: Participants needed to meet the eligibility criteria including a HbA1c level between 6.5% and 9.9%. Randomization was 1:1 to a 3-month intervention that consisted of nursing-led diabetes education and immediate initiation of metformin versus referral to primary care for usual care (control). RESULTS: Three hundred and seventy nine patients were screened using EHR, 55 agreed to participate, and 3 had eligible HbA1c levels and were randomized in the study. Primary reasons for study exclusion included life expectancy ≤2 years (16.9%), current use or inability to tolerate metformin (14.8%), and abnormal labs that contraindicated metformin use (13.9%). CONCLUSION: This study was not feasible due to recruitment inefficiencies, but acceptable to all who qualified.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Neoplasias , Adulto , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Projetos Piloto , Estudos de Viabilidade , Hemoglobinas Glicadas , Papel do Profissional de Enfermagem , Metformina/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico
3.
Future Oncol ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36399037

RESUMO

Immune checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not clinically effective in immunogenically 'cold' tumors such as pancreatic cancer, prostate cancer and neuroendocrine tumors. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade in tumors that have traditionally shown a lack of clinical response to immunotherapy. This signal-seeking, single-arm, prospective clinical trial aims to determine the objective response of tivozanib and atezolizumab in advanced immunogenically cold solid tumors. Clinical Trial Registration: NCT05000294 (ClinicalTrials.gov).

4.
Expert Opin Pharmacother ; 23(10): 1135-1142, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35848061

RESUMO

INTRODUCTION: Renal cell carcinoma (RCC) accounts for 2.4% of cancers, with clear cell kidney cancer being the most common histologic subtype. Despite recent therapeutic advances, the prognosis for patients with advanced disease remains poor, with a 5-year survival rate of only 13.9% reported in the United States. Tivozanib is a novel inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1, -2, and -3 and has recently been approved by the US FDA for use in patients with relapsed or recurrent advanced RCC following two or more prior systemic therapies. AREAS COVERED: Here, the authors provide a review focusing on the development of tivozanib, compare tivozanib to other agents in the VEGFR inhibitor class, detail how tivozanib fits into current treatment landscape, and describe ongoing studies involving this agent. EXPERT OPINION: Given tivozanib's excellent safety profile and demonstrated clinical benefit in patients with pretreated disease, tivozanib is likely to be heavily utilized in the later-line setting. The ongoing TINIVO-2 study may further impact the treatment landscape by evaluating the use of tivozanib plus nivolumab in patients who have progressed on an immune checkpoint inhibitor.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Quinolinas , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular , Fator A de Crescimento do Endotélio Vascular
5.
Clin Genitourin Cancer ; 20(3): 252-259, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35249821

RESUMO

INTRODUCTION: The ligation of the interleukin-2 (IL-2) receptor and immune checkpoint blockade may each alter lymphocytes, thereby inducing regression in various cancers. Single agent objective response rates of 14% to 25% have been reported for usual schedule 14-dose-in-a-row IL-2 therapy of metastatic clear cell renal cancer (ccRCC), with a notable subset of responses being durable. Pembrolizumab yielded a 33% response rate in patients with metastatic ccRCC. PATIENTS AND METHODS: This study addressed the safety and feasibility of the combination of IL-2 and pembrolizumab in the treatment of metastatic ccRCC. Subjects were treated with four 9-week blocks of therapy, receiving pembrolizumab every 3 weeks in all blocks and receiving 4 courses of 5-planned-doses high dose IL-2 in each of blocks 2 and 3. Safety was monitored by a Pocock boundary of study suspension and re-evaluation if exceeding a 15% dose limiting toxicity rate at α = 0.05. The Simon 2-stage design tested for an alternative hypothesis response rate of at least a 45% vs. a null hypothesis rate of less than 20%, with α = 0.10 and 90% power RESULTS: No accrual suspension for safety was triggered. The objective response rate was 70% (19/27, 95% CI: 0.50-0.86). Nine patients responded after pembrolizumab alone and ten responded after the addition of IL-2. At a minimum follow-up of 23 months, 9 of the responding patients had no disease progression requiring additional treatment. CONCLUSION: The combination of 5-planned-dose-schedule high dose IL-2 and pembrolizumab is feasible, with a high response rate, justifying further exploration of this dual immune treatment of metastatic ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Anticorpos Monoclonais Humanizados , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Interleucina-2 , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia
6.
Cancers (Basel) ; 15(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36612164

RESUMO

Muscle-invasive bladder cancer is a life-threatening disease best managed with multimodal therapy. Neoadjuvant chemotherapy prior to cystectomy significantly improves survival with the greatest benefit noted in patients with a complete pathologic response noted at cystectomy. While radical cystectomy is currently an important part of the treatment plan, surgical morbidity remains high. Accurate prediction of complete responses to chemotherapy would enable avoiding the morbidity of radical cystectomy. Multiple clinical, pathologic, molecular, and radiographic predictors have been evaluated. Clinical and standard pathologic findings have not been found to be accurate predictors of complete response. To date, tumor genomic findings have been the most promising and have led to multiple clinical trials to evaluate if bladder preservation is possible in select patients. Radiomics has shown initial promise with larger validation series needed. These predictors can be further characterized as treatment specific and non-treatment specific. With the potential changing landscape of neoadjuvant therapy prior to radical cystectomy and the limitations of individual predictors of a complete response, a panel of several biomarkers may enhance patient selection for bladder preservation. The aim of this review is to summarize predictors of complete response to neoadjuvant chemotherapy.

7.
Cancers (Basel) ; 13(22)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34831009

RESUMO

Several clinicopathological features of clear cell renal cell carcinomas (ccRCC) contribute to make an "atypical" cancer, including resistance to chemotherapy, sensitivity to anti-angiogenesis therapy and ICIs despite a low mutational burden, and CD8+ T cell infiltration being the predictor for poor prognosis-normally CD8+ T cell infiltration is a good prognostic factor in cancer patients. These "atypical" features have brought researchers to investigate the molecular and immunological mechanisms that lead to the increased T cell infiltrates despite relatively low molecular burdens, as well as to decipher the immune landscape that leads to better response to ICIs. In the present study, we summarize the past and ongoing pivotal clinical trials of immunotherapies for ccRCC, emphasizing the potential molecular and cellular mechanisms that lead to the success or failure of ICI therapy. Single-cell analysis of ccRCC has provided a more thorough and detailed understanding of the tumor immune microenvironment and has facilitated the discovery of molecular biomarkers from the tumor-infiltrating immune cells. We herein will focus on the discussion of some major immune cells, including T cells and tumor-associated macrophages (TAM) in ccRCC. We will further provide some perspectives of using molecular and cellular biomarkers derived from these immune cell types to potentially improve the response rate to ICIs in ccRCC patients.

8.
JCO Oncol Pract ; 17(5): 240-245, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33710933

RESUMO

Patients with autoimmune disorders, multiple comorbidities, poor performance status, advanced age, and infection with SARS-CoV-2 (COVID-19) each represent unique subgroups of patients with cancer to whom little is known of the effects, benefits, and complications of checkpoint inhibitor (CPI) therapy. Although prospective trials are lacking in these populations, retrospective data and cohort series suggest that these patients can safely receive and benefit from CPI therapy. Here, we review the relevant data available and offer clinical recommendations in managing these complex patients with CPI therapy, where otherwise indicated.


Assuntos
COVID-19 , Neoplasias , Humanos , Imunoterapia , Neoplasias/terapia , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2
9.
Future Sci OA ; 6(1): FSO437, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31915536

RESUMO

AIM: Radium-223 improves overall survival in patients with metastatic castration-resistant prostate cancer to the bone. Radium-223 causes double-strand DNA breaks and produces γH2AX, a potential biomarker for response. We examined the feasibility of tracking γH2AX positivity and numeration in circulating tumor cells. PATIENTS & METHODS: Ten patients with biopsy-confirmed symptomatic M1b castration-resistant prostate cancer received radium-223 as standard of care and were assessed for γH2AX level changes following doses 1, 3 and 6. RESULTS: Trend tests confirmed that patients with ≥50% increase in circulating tumor cells positive for γH2AX postradium-223 therapy had a lower risk of death (p = 0.035). CONCLUSION: Regular interval measurements of γH2AX are feasible. The potential correlation between γH2AX changes and overall survival warrants further investigation.

10.
Head Neck Pathol ; 11(3): 338-345, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28025779

RESUMO

Determine if highly proliferative head and neck squamous cell carcinomas, assessed by pretreatment Ki-67 expression, respond more robustly to induction chemotherapy (IC) that is selectively toxic to cycling cells. Retrospective analysis of 59 patients treated with IC and chemoradiation. IC included either nab-paclitaxel, cisplatin, 5-FU and cetuximab (APF-C, n = 27) or docetaxel, cisplatin, 5-FU +/- cetuximab (TPF+/-C, n = 32). Ki-67 expression was assessed by immunohistochemistry. Tumor response (complete/partial/stable/progressive) at the primary site after two IC cycles was evaluated by visual examination in all patients. In the APF-C sub-group, tumor response (primary site and neck nodes) after two IC cycles was evaluated by computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT. Ki-67 expression (median 66%, range: 16-97) did not differ across the tumor response categories assessed by visual examination (p = 0.95), CT (p = 0.30), or FDG-PET/CT (p = 0.65). Median decrease in summed SUVmax of measured lesions was 71.6% (range: 8.3-100%). The Pearson correlation coefficient between Ki-67 expression and the percent decrease in summed SUVmax was 0.48 (p = 0.02). Ki-67 expression was not different between those with or without a relapse (median: 60 and 71%, p = 0.10). In multivariate regression analysis (MVA) controlling for p16 positive oropharyngeal SCC status and smoking status, Ki-67 expression was not significantly associated with tumor response by visual examination (coefficient estimate -0.002, standard error 0.010, p = 0.84), CT (coefficient estimate -0.007, standard error 0.011, p = 0.54), FDG-PET/CT (coefficient estimate 0.006, standard error 0.008, p = 0.51), the percent decrease in summed SUVmax (coefficient estimate 0.389, standard error 0.222, p = 0.09), or relapse events (OR = 1.02(95%CI:0.99-1.05), p = 0.28). No significant relationships were found in MVA between pretreatment Ki-67 expression and tumor response to IC or to relapse.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Quimioterapia de Indução/métodos , Antígeno Ki-67/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/análise , Cetuximab/administração & dosagem , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxoides/administração & dosagem , Resultado do Tratamento , Adulto Jovem
11.
Ann Am Thorac Soc ; 11(6): 874-81, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24956379

RESUMO

RATIONALE: Multiple causes for air trapping as identified by expiratory computed tomography (CT) have been reported, but a unified evaluation schema has never been proposed. OBJECTIVES: It was our purpose to identify imaging features that would help distinguish etiologies of mosaic air trapping. METHODS: Cases with the term "air trapping" in the radiology report in 2010 were identified by searching the Radiology Information System of an academic tertiary care center and associated community hospital. Medical records and CT examinations were reviewed for the causes of air trapping. MEASUREMENTS AND MAIN RESULTS: Causes for moderate to severe air trapping could be identified in 201 of 230 (87.4%) cases and could be subdivided into those associated with bronchiectasis (76 of 201, 38%), those associated with interstitial lung disease (62 of 201, 31%), those associated with tree-in-bud opacities (5 of 201, 2%), and those with air trapping alone (58 of 201, 29%). When found with bronchiectasis, nontuberculous mycobacteria, cystic fibrosis, idiopathic bronchiectasis, and transplant-related bronchiolitis obliterans were the most common causes of air trapping. When found with interstitial lung disease, sarcoidosis, hypersensitivity pneumonitis, or unspecified interstitial lung disease were the most common cause of air trapping. When found in isolation, chronic bronchitis, asthma, bronchiolitis obliterans, and unspecified small airways disease were the most common causes of air trapping. Unusual conditions causing isolated air trapping included vasculitis and diffuse idiopathic neuroendocrine cell hyperplasia. CONCLUSION: A variety of conditions can cause air trapping. Associated imaging findings can narrow the differential diagnosis.


Assuntos
Asma/diagnóstico por imagem , Bronquiectasia/diagnóstico por imagem , Fibrose Cística/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Asma/fisiopatologia , Bronquiectasia/fisiopatologia , Bronquiolite Obliterante , Fibrose Cística/fisiopatologia , Diagnóstico Diferencial , Humanos , Pulmão/fisiopatologia , Curva ROC , Reprodutibilidade dos Testes , Testes de Função Respiratória , Estudos Retrospectivos
12.
Pediatr Radiol ; 42(4): 481-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22218736

RESUMO

We report the use of susceptibility-weighted imaging (SWI) in detection of red nucleus (rubral) degeneration and atrophy in children with hypertrophic olivary degeneration (HOD) after posterior fossa tumor resection. The use of this modality for this particular application has not been previously described. Detection of red nucleus changes seems to be facilitated by the contrast mechanism of SWI over conventional MRI sequences. SWI can be considered in the evaluation of these patients and in the future might provide a means for further classification of patients with HOD and related symptomatology.


Assuntos
Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/cirurgia , Imageamento por Ressonância Magnética/métodos , Núcleo Olivar/patologia , Núcleo Rubro/patologia , Adolescente , Humanos , Hipertrofia/patologia , Masculino , Complicações Pós-Operatórias , Resultado do Tratamento
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