RESUMO
PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (nâ¯=â¯58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (nâ¯=â¯26) had comparatively lower rates of pelvic nodal (16.7%, pâ¯=â¯0.002) and nodal-only (19.2%, pâ¯=â¯0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.
Assuntos
Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prostatectomia , Neoplasias da Próstata , Terapia de Salvação , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Estudos Retrospectivos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Fatores de Risco , Metástase Linfática , Pelve/diagnóstico por imagem , Pelve/efeitos da radiação , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/efeitos da radiação , Lisina/análogos & derivados , Ureia/análogos & derivadosRESUMO
PURPOSE: Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy. PATIENTS AND METHODS: Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate. RESULTS: From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; Pone-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo (Ptwo-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period. CONCLUSION: Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.
Assuntos
Carcinoma de Células Renais , Indazóis , Neoplasias Renais , Metastasectomia , Pirimidinas , Sulfonamidas , Humanos , Indazóis/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/mortalidade , Pirimidinas/uso terapêutico , Pirimidinas/farmacologia , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Neoplasias Renais/patologia , Neoplasias Renais/tratamento farmacológico , Método Duplo-Cego , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Inibidores da Angiogênese/uso terapêutico , Intervalo Livre de Doença , Idoso de 80 Anos ou maisRESUMO
Cancer immunotherapy tools include antibodies, vaccines, cytokines, oncolytic viruses, bispecific molecules, and cellular therapies. This review will focus on adoptive cellular therapy, which involves the isolation of a patient's own immune cells followed by their ex vivo expansion and reinfusion. The majority of adoptive cellular therapy strategies utilize T cells isolated from tumor or peripheral blood, but may utilize other immune cell subsets. T-cell therapies in the form of tumor-infiltrating lymphocytes, T-cell receptor T cells, and CAR T cells may act as "living drugs" as these infused cells expand, engraft, and persist in vivo, allowing adaptability over time and enabling durable remissions in subsets of patients. Adoptive cellular therapy has been less successful in the management of solid tumors because of poor homing, proliferation, and survival of transferred cells. Strategies are discussed, including expression of transgenes to address these hurdles. Additionally, advances in gene editing using CRISPR/Cas9 and similar technologies are described, which allow for clinically translatable gene-editing strategies to enhance the antitumor activity and to surmount the hostilities advanced by the host and the tumor. Finally, the common toxicities and approaches to mitigate these are reviewed.
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Imunoterapia Adotiva , Neoplasias , Humanos , Linfócitos do Interstício Tumoral , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos TRESUMO
PURPOSE: To validate currently used recurrence prediction models for renal cell carcinoma (RCC) by using prospective data from the ASSURE (ECOG-ACRIN E2805; Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) adjuvant trial. PATIENTS AND METHODS: Eight RCC recurrence models (University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Leibovich; Kattan; Memorial Sloan Kettering Cancer Center [MSKCC]; Yaycioglu; Karakiewicz; and Cindolo) were selected on the basis of their use in clinical practice and clinical trial designs. These models along with the TNM staging system were validated using 1,647 patients with resected localized high-grade or locally advanced disease (≥ pT1b grade 3 and 4/pTanyN1Mo) from the ASSURE cohort. The predictive performance of the model was quantified by assessing its discriminatory and calibration abilities. RESULTS: Prospective validation of predictive and prognostic models for localized RCC showed a substantial decrease in each of the predictive abilities of the model compared with their original and externally validated discriminatory estimates. Among the models, the SSIGN score performed best (0.688; 95% CI, 0.686 to 0.689), and the UISS model performed worst (0.556; 95% CI, 0.555 to 0.557). Compared with the 2002 TNM staging system (C-index, 0.60), most models only marginally outperformed standard staging. Importantly, all models, including TNM, demonstrated statistically significant variability in their predictive ability over time and were most useful within the first 2 years after diagnosis. CONCLUSION: In RCC, as in many other solid malignancies, clinicians rely on retrospective prediction tools to guide patient care and clinical trial selection and largely overestimate their predictive abilities. We used prospective collected adjuvant trial data to validate existing RCC prediction models and demonstrate a sharp decrease in the predictive ability of all models compared with their previous retrospective validations. Accordingly, we recommend prospective validation of any predictive model before implementing it into clinical practice and clinical trial design.
Assuntos
Carcinoma de Células Renais/epidemiologia , Neoplasias Renais/epidemiologia , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Recidiva Local de Neoplasia , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Projetos de PesquisaRESUMO
Recent adjuvant vascular endothelial growth factor tyrosine kinase inhibitor trials in resected high-risk renal cell carcinoma that compared sunitinib, sorafenib, pazopanib, and axitinib with placebo controls have demonstrated mixed impact on disease-free survival, no improvement in overall survival, and, thus, controversy. Here, we discuss the results and conduct of these trials to provide new insight into the goals and strategies of treating resected renal cell cancer that is at high risk for recurrence. The potential for leveraging what we have learned from these trials to conduct successful contemporary adjuvant and perioperative immune checkpoint inhibition trials and future adjuvant trial design is discussed.
RESUMO
Recent advances in advanced renal cell cancer (RCC) research have produced new drugs and therapies for patients with metastatic disease leading to higher response rates, improvements in progression-free survival, and longer overall survival. These advances have yet to be realized in patients with early-stage kidney cancer, and to date, no drug has been approved for the adjuvant treatment of localized kidney cancer. The current standard of care for localized high-risk kidney cancers is resection of the primary tumor. Here, we review the results of recently completed adjuvant vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) trials in RCC that have been reported, or are awaiting results. Further, we discuss the new immune checkpoint inhibitor adjuvant trials planned. There is hope that these trials may lead to new options and longer survival for patients with localized high-risk kidney cancer.
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Carcinoma de Células Renais/terapia , Imunoterapia/métodos , Fator A de Crescimento do Endotélio Vascular/imunologia , Carcinoma de Células Renais/patologia , HumanosRESUMO
OBJECTIVE: Previous studies evaluating the effect of metformin on cancer risk have been impacted by time-related biases. To avoid these biases, we examined the incidence of bladder cancer in new users of metformin and sulfonylureas (SUs). RESEARCH DESIGN AND METHODS: This cohort study included 87,600 patients with type 2 diabetes in The Health Improvement Network database. Use of metformin or an SU was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared metformin use with SU use, adjusted for age, sex, smoking, obesity, and HbA1c level. RESULTS: We identified 196 incident bladder cancers in the metformin cohort and 66 cancers in the SU cohort. Use of metformin was not associated with decreased bladder cancer risk (HR 0.81 [95% CI 0.60-1.09]). This association did not differ by sex (P for interaction = 0.20). We observed no association with duration of metformin relative to SU use (3 to <4 years of use: 0.57 [0.25-1.34]; 4 to <5 years of use: 0.93 [0.30-2.85; ≥5 years of use: 1.18 [0.44-3.19]; P for trend = 0.26). CONCLUSIONS: Use of metformin is not associated with a decreased incidence of bladder cancer. Similar methods should be used to study other cancers that have previously been identified as potentially preventable with metformin.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Neoplasias da Bexiga Urinária/epidemiologia , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Hipoglicemiantes/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/patologia , Estudos RetrospectivosRESUMO
Inherited susceptibility to kidney cancer is a fascinating and complex topic. Our knowledge about types of genetic syndromes associated with an increased risk of disease is continually expanding. Currently, there are 10 syndromes associated with an increased risk of all types of kidney cancer, which are reviewed herein. Clear cell kidney cancer is associated with von Hippel Lindau disease, chromosome 3 translocations, PTEN hamartomatous syndrome, and mutations in the BAP1 gene as well as several of the genes encoding the proteins comprising the succinate dehydrogenase complex (SDHB/C/D). Type 1 papillary kidney cancers arise in conjunction with germline mutations in MET and type 2 as part of hereditary leiomyomatosis and kidney cell cancer (fumarate hydratase [FH] mutations). Chromophone and oncocytic kidney cancers are predominantly associated with Birt-Hogg-Dubé syndrome. Patients with Tuberous Sclerosis Complex (TSC) commonly have angiomyolipomas and rarely their malignant counterpart epithelioid angiomyolipomas. The targeted therapeutic options for the kidney cancer associated with these diseases are just starting to expand and are an area of active clinical research.