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Molten salts serve as effective high-temperature heat transfer fluids and thermal storage media used in a wide range of energy generation and storage facilities, including concentrated solar power plants, molten salt reactors and high-temperature batteries. However, at the salt-metal interfaces, a complex interplay of charge-transfer reactions involving various metal ions, generated either as fission products or through corrosion of structural materials, takes place. Simultaneously, there is a mass transport of ions or atoms within the molten salt and the parent alloys. The precise physical and chemical mechanisms leading to the diverse morphological changes in these materials remain unclear. To address this knowledge gap, this work employed a combination of synchrotron X-ray nanotomography and electron microscopy to study the morphological and chemical evolution of Ni-20Cr in molten KCl-MgCl2, while considering the influence of metal ions (Ni2+, Ce3+, and Eu3+) and variations in salt composition. Our research suggests that the interplay between interfacial diffusivity and reactivity determines the morphological evolution. The summary of the associated mass transport and reaction processes presented in this work is a step forward toward achieving a fundamental comprehension of the interactions between molten salts and alloys. Overall, the findings offer valuable insights for predicting the diverse chemical and structural alterations experienced by alloys in molten salt environments, thus aiding in the development of protective strategies for future applications involving molten salts.
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OBJECTIVES: Active surveillance (AS) is a management strategy for patients with favorable risk prostate cancer. Multi-parametric magnetic resonance imaging (mpMRI) may impact upgrading rates, but there is mixed evidence on the appropriate timing to introduce mpMRI. We evaluated timing of initial mpMRI use for patients on AS and compared upgrading and intervention rates for AS candidates who received initial mpMRI before diagnostic biopsy vs. confirmatory biopsy. SUBJECTS AND METHODS: Patients enrolled in AS captured by the Prospective Loyola Urology mpMRI (PLUM) Prostate Biopsy Cohort which captures men undergoing MRI-fusion prostate biopsy. We included patients enrolled in AS between January 2014 and October 2022. We conducted a retrospective analysis of patients who underwent MRI-fusion prostate biopsy while on AS at our institution. The cohort was stratified by men who underwent first mpMRI prior to diagnostic biopsy (MRI-DBx), confirmatory biopsy (MRI-CBx), or a subsequent surveillance biopsy. Oncologic outcomes including pathologic reclassification, intervention-free survival, progression-free survival, and overall survival were evaluated. RESULTS: Of 346 patients identified on AS, 94 (27.2%) received mpMRI at the time of diagnostic biopsy, 182 (52.6%) at confirmatory biopsy, and 70 (20.2%) at a later biopsy. At confirmatory biopsy (median 14 months), there was no difference in upgrading (HR 0.95, Pâ¯=â¯0.78) or intervention rates (HR 0.97, Pâ¯=â¯0.88) between MRI-DBx and MRI-CBx. PI-RADS score on initial mpMRI was associated with upgrading during AS follow-up relative to men with negative mpMRI (HR 4.20 (Pâ¯=â¯0.04), 3.24 (P < 0.001), and 1.99 (P < 0.001) for PI-RADS 5, 4, and 3, respectively), and PSA density was associated with intervention (HR 1.52, Pâ¯=â¯0.03). CONCLUSION: mpMRI can serve as a prognostic tool to select and monitor AS patients, but there was no difference in upgrading or intervention rates based on initial timing of MRI.
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Biópsia Guiada por Imagem , Neoplasias da Próstata , Conduta Expectante , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Conduta Expectante/métodos , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Próstata/patologia , Próstata/diagnóstico por imagemRESUMO
PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.
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Vacina BCG , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/mortalidade , Masculino , Feminino , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Administração Intravesical , Seguimentos , Idoso , Pessoa de Meia-Idade , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Carcinoma in Situ/tratamento farmacológico , Invasividade Neoplásica , Resultado do Tratamento , Adenoviridae/genética , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
We aim to compare complications, readmission, survival, and prescribing patterns of opioids for post-operative pain management for Robotic-assisted laparoscopic radical cystectomy (RARC) as compared to open radical cystectomy (ORC). Patients that underwent RARC or ORC for bladder cancer at a tertiary care center from 2005 to 2021 were included. Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier curves and multivariable Cox proportional hazards regression models. Comparisons of narcotic usage were completed with oral morphine equivalents (OMEQ). Multivariable linear regression was used to assess predictors of OMEQ utilization. A total of 128 RARC and 461 ORC patients were included. There was no difference in rates of Clavien-Dindo grade ≥ 3 complications between RARC and ORC (36.7 vs 30.1%, p = 0.16). After a mean follow up of 3.4 years, RFS (HR 0.96, 95%CI 0.58-1.56) and OS (HR 0.69, 95%CI 0.46-1.05) were comparable between RARC and ORC. There was no difference in the narcotic usage between patients in the RARC and ORC groups during the last 24 h of hospitalization (median OMEQ: 0 vs 0, p = 0.33) and upon discharge (median OMEQ: 178 vs 210, p = 0.36). Predictors of higher OMEQ discharge prescriptions included younger age [(- )3.46, 95%CI (-)5.5-(-)0.34], no epidural during hospitalization [- 95.85, 95%CI (- )144.95-(- )107.36], and early time-period of surgery [(- )151.04, 95%CI (- )194.72-(- )107.36]. RARC has comparable 90-day complication rates and early survival outcomes to ORC and remains a viable option for bladder cancer. RARC results in comparable levels of opioid utilization for pain management as ORC.
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Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/efeitos adversos , Cistectomia/métodos , Analgésicos Opioides/uso terapêutico , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Padrões de Prática Médica , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , EntorpecentesRESUMO
INTRODUCTION: We aimed to assess utilization of neoadjuvant chemotherapy (NAC) and etiologies for lack of NAC receipt among patients with muscle-invasive bladder cancer (MIBC). METHODS: Patients diagnosed with MIBC undergoing radical cystectomy at a single institution (2005-2021) were included. Patients were categorized by receipt of NAC, and reasons for no NAC were categorized into eligibility and elective factors. Overall survival was analyzed using univariable and multivariable Cox proportional hazards regression models and modeled with Kaplan-Meier curves. RESULTS: Three hundred eighty patients with MIBC were included; 154 (40.5%) received NAC. Patients were not candidates for NAC due to renal dysfunction (16.6%), clinical contraindications (4.7%), salvage setting (2.1%), and histology (5.3%; total N = 109). Among 271 (71.3%) who were eligible, utilization increased from early (2005-2016) to recent (2016-2021) time periods (34.2% to 85.7% among NAC-eligible, P < .001; 22.8% vs 67.1% among all MIBC, P < .001). Elective factors for not receiving NAC included patient symptoms (7.8%), disease progression concern (7.0%), patient preference/refusal (20.3%) and provider discretion (8.1%) among 271 NAC-eligible patients. Notably, patient preference/refusal decreased from 33.6% to 3.4% in recent years (P < .001). On multivariable analysis, lack of NAC utilization due to renal dysfunction (HR 2.18, P = .002), clinical contraindications (HR 2.62, P = .01), and elective factors (HR 1.88, P = .01) were associated with worse overall survival. CONCLUSIONS: NAC utilization increased over time with 85.7% of eligible patients with MIBC receiving NAC in recent years. Renal dysfunction, patient preference, and clinical contraindications were primary etiologies for lack of NAC. Fewer patients refused NAC in recent years leading to a potential ceiling for NAC utilization.
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Nefropatias , Neoplasias da Bexiga Urinária , Humanos , Terapia Neoadjuvante/efeitos adversos , Cistectomia/efeitos adversos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Músculos/patologiaRESUMO
Objectives: To describe and compare the incidence, stage at diagnosis, and survival for genitourinary cancers in the border regions and in Hispanic-Americans. Materials and methods: A population-based search was performed using the Surveillance, Epidemiology, and End Results Program 18 database and the Texas Cancer Registry from 2000 to 2017. Cox regression models were performed with adjusted for age, gender, race, cancer type, cancer stage, insurance status, and cause of death were used to compare cancer-specific survival. Results: A total of 63,236 kidney and renal pelvis, 38,398 bladder, 170,640 prostate, 24,313 testicular cancer cases were identified. Cancer-specific survival was found to be improved in Hispanic-Americans in kidney and renal pelvis (hazard ratio [HR], 0.903, 95% confidence interval [CI], 0.856-0.952, p = 0.0001), and bladder cancers (HR, 0.817, 95% CI, 0.743-0.898, p < 0.001), despite a more advanced stage at diagnosis in Hispanics with bladder cancer (p < 0.0074). Testicular cancer has a survival disadvantage for individuals living in the border region (HR, 1.315, 95% CI, 1.124-1.539, p = 0.0006). Conclusions: Disparities exist between Hispanic-Americans and Non-Hispanic White and also between individuals living in the border counties when compared to other regions. This is most significant in individuals with testicular cancer residing in the border region who demonstrate worse overall survival.
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The fate of fission-product iodine is critical for the deployment of next generation molten salt reactor technologies, owing to its volatility and biological impacts if it were to be released into the environment. To date, little is known on how ionizing radiation fields influence the redox chemistry, speciation, and transport of iodine in high temperature molten salts. Here we employ picosecond electron pulse irradiation techniques to elucidate for the first time the impact of iodide ions (I-) on the speciation and chemical kinetics of the primary radiation-induced transient radicals generated in molten chloride salt mixtures (eS- and Cl2Ë-) as a function of temperature (400-700 °C). In the presence of I- ions (≥ 1 wt% KI in LiCl-KCl eutectic), we find that the transient spectrum following the electron pulse is composed of at least three overlapping species: the eS- and the Cl2Ë- and IClË- radical anions, for which a deconvoluted spectrum of the latter is reported here for the first time in molten salts. This new transient spectrum was consistent with gas phase density functional theory calculations. The lifetime of the eS- was unaffected by the addition of I- ions. The newly observed interhalogen radical anion, IClË-, exhibited a lifetime on the order of microseconds over the investigated temperature range. The associated chemical kinetics indicate that the predominate mechanism of IClË- decay is via reaction with the Cl2Ë- radical anion. The iodine containing product of this reaction is expected to be ICl2-, which will have implications for the transport of fission-product iodine in MSR technologies.
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Lanthanides are important fission products in molten salt reactors, and understanding their structure and that of their mixtures is relevant to many scientific and technological problems including the recovery and separation of rare earth elements using molten salt electrolysis. The literature on molten salts and specifically on LaCl3 and LaCl3-NaCl mixtures is often fragmented, with different experiments and simulations coinciding in their explanation for certain structural results but contradicting or questioning for others. Given the very practical importance that actinide and lanthanide salts have for energy applications, it is imperative to arrive at a clear unified picture of their local and intermediate-range structure in the neat molten state and when mixed with other salts. This article aims to unequivocally answer a set of specific questions: is it correct to think of long-lived octahedral coordination structures for La3+? What is the nature as a function of temperature of networks and intermediate-range order particularly upon dilution of the trivalent ion salt? Is the so-called scattering first sharp diffraction peak (FSDP) for neat LaCl3 truly indicative of intermediate-range order? If so, why is there a new lower-q peak when mixed with NaCl? Are X-ray scattering and Raman spectroscopy results fully consistent and easily described by simulation results? We will show that answers to these questions require that we abandon the idea of a most prominent coordination state for M3+ ions and instead think of multiple competing coordination states in exchange due to significant thermal energy in the molten state.
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Elementos da Série dos Lantanídeos , Sais , Sais/química , Cloreto de Sódio , Íons/química , TemperaturaRESUMO
PURPOSE: Sarcomatoid dedifferentiation in renal cell carcinoma (RCC) represents an aggressive histology where degree of sarcomatoid histology (SH) may impact prognosis for cM0 and cM1 patients. We aimed to evaluate the association of percentage of SH with survival. MATERIALS AND METHODS: Patients ≥18 years old diagnosed with RCC with any degree of SH after nephrectomy were included (2005-2020) from a single-center. Associations of degree of SH and cM stage with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: One hundred twenty-eight patients were included with 80 (62.5%) cM0 and 48 (37.5%) cM1. cM1 patients were more likely to be male with higher clinical T stage (Pâ¯=â¯0.001) than cM0, but a similar proportion had ≥20% SH (47.9% vs. 42.5%, Pâ¯=â¯0.55). With median 19.4 months follow-up, SH was associated with worse OS per 10% increase (hazard ratio [HR] 1.12 [95% confidence interval {CI} 1.03-1.23], Pâ¯=â¯0.009) and a ≥20% cutoff (HR 2.87 [95% CI 1.27-6.47], Pâ¯=â¯0.01). Patients with cM0 disease and <20% SH had better 2-year OS (81.4%) compared to cM0 and ≥20% SH (44.8%) or cM1 patients who received nephrectomy (54.8%). Tumor size was also an independent predictor. Sites of distant metastasis and lines of therapy were similar for metachronous and synchronous patients. SH stratified 2-year RFS (cM0: 70.2% for <20% SH vs. 32.1% for ≥20% SH). CONCLUSIONS: SH in RCC is independently associated with OS and RFS. Patients who are cM0 with any SH may be candidates for adjuvant immunotherapy while those with ≥20% SH likely carry micrometastatic disease and should receive closer surveillance.
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Carcinoma de Células Renais , Neoplasias Renais , Sarcoma , Adolescente , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Nefrectomia , Prognóstico , Estudos Retrospectivos , Sarcoma/patologiaRESUMO
Importance: No data exist on time to recovery of patient-reported and performance-related measures of functional independence after radical cystectomy (open or robotic). Objective: To determine recovery of functional independence after radical cystectomy and whether robot-assisted radical cystectomy (RARC) is associated with any advantage over open procedures. Design, Setting, and Participants: Data for this secondary analysis from the RAZOR (Randomized Open vs Robotic Cystectomy) trial were used. RAZOR was a phase 3 multicenter noninferiority trial across 15 academic medical centers in the US from July 1, 2011, to November 18, 2014, with a median follow-up of 2 years. Participants included the per-protocol population (n = 302). Data were analyzed from February 1, 2017, to May 1, 2021. Interventions: Robot-assisted radical cystectomy or open radical cystectomy (ORC). Main Outcomes and Measures: Patient-reported (activities of daily living [ADL] and independent ADL [iADL]) and performance-related (hand grip strength [HGS] and Timed Up & Go walking test [TUGWT]) measures of independence were assessed. Patterns of postoperative recovery for the entire cohort and comparisons between RARC and ORC were performed. Exploratory analyses to assess measures of independence across diversion type and to determine whether baseline impairments were associated with 90-day complications or 1-year mortality were performed. Findings: Of the 302 patients included in the analysis (254 men [84.1%]; mean [SD] age at consent, 68.0 [9.7] years), 150 underwent RARC and 152 underwent ORC. Baseline characteristics were similar in both groups. For the entire cohort, ADL, iADL, and TUGWT recovered to baseline by 3 postoperative months, whereas HGS recovered by 6 months. There was no difference between RARC and ORC for ADL, iADL, TUGWT, or HGS scores at any time. Activities of daily living recovered 1 month after RARC (mean estimated score, 7.7 [95% CI, 7.3-8.0]) vs 3 months after ORC (mean estimated score, 7.5 [95% CI, 7.2-7.8]). Hand grip strength recovered by 3 months after RARC (mean estimated HGS, 29.0 [95% CI, 26.3-31.7] kg) vs 6 months after ORC (mean estimated HGS, 31.2 [95% CI, 28.8-34.2] kg). In the RARC group, 32 of 90 patients (35.6%) showed a recovery in HGS at 3 months vs 32 of 88 (36.4%) in the ORC group (P = .91), indicating a rejection of the primary study hypothesis for HGS. Independent ADL and TUGWT recovered in 3 months for both approaches. Hand grip strength showed earlier recovery in patients undergoing continent urinary diversion (mean HGS at 3 months, 31.3 [95% CI, 27.7-34.8] vs 33.9 [95% CI, 30.5-37.3] at baseline; P = .09) than noncontinent urinary diversion (mean HGS at 6 months, 27.4 [95% CI, 24.9-30.0] vs 29.5 [95% CI, 27.2-31.9] kg at baseline; P = .02), with no differences in other parameters. Baseline impairments in any parameter were not associated with 90-day complications or 1-year mortality. Conclusions and Relevance: The results of this secondary analysis suggest that patients require 3 to 6 months to recover baseline levels after radical cystectomy irrespective of surgical approach. These data will be invaluable in patient counseling and preparation. Hand grip strength and ADL tended to recover to baseline earlier after RARC; however, there was no difference in the percentage of patients recovering when compared with ORC. Further study is needed to assess the clinical significance of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT01157676.
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Atividades Cotidianas , Cistectomia/métodos , Recuperação de Função Fisiológica , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Resultado do Tratamento , Estados UnidosRESUMO
A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.
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Antineoplásicos , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Feminino , Humanos , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
PURPOSE: To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer. METHODS: Patients with clinical T2-4aN0/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg/m2 once on day 1, and gemcitabine 1,000 mg/m2 once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg/m2 once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (< pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored. RESULTS: Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved < pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients. CONCLUSION: Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Cistectomia , Desoxicitidina/análogos & derivados , Inibidores de Checkpoint Imunológico/administração & dosagem , Terapia Neoadjuvante , Neoplasias da Bexiga Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/efeitos adversos , Cistectomia/efeitos adversos , Cistectomia/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Invasividade Neoplásica , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Fatores de Tempo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , GencitabinaRESUMO
OBJECTIVE: To characterize post-orchiectomy treatment trends in prepubescent and adolescent patients with nonseminomatous germ cell tumors (NSGCT) and identify patient and hospital factors associated with receiving surveillance or treatment (chemotherapy or RPLND) after orchiectomy. METHODS: Patients <18 years old diagnosed with NSGCT from 2006 to 2016 were extracted from the National Cancer Database. Patients were stratified into prepubescent (<12 years old) and adolescent (age 13-17) cohorts. National trends and multivariable logistic regression for odds of undergoing treatment were identified. RESULTS: Documentation of use of post-orchiectomy treatment or surveillance was available for 1006 patients. This population was divided into a prepubescent cohort (≤12 years of age, n = 153) and an adolescent cohort (13-17 years of age, n = 853). 545 (54.4%) patients proceeded with treatment. The proportion of patients undergoing treatment in each cohort remained similar over time, but there was a shift in the adolescent cohort away from RPLND towards chemotherapy. In the prepubescent cohort, pathologic stage group III was associated with undergoing treatment. Older age, >50 miles travel to treatment facility, and higher pathologic stage group were associated with treatment in the adolescent cohort. Black race was associated with decreased odds of undergoing treatment among adolescents. CONCLUSION: National treatment trends regarding NSGCT remained similar over a decade. Higher disease stage in prepubescent patients lead to additional post-orchiectomy treatment. Adolescents with NSGCT were more likely to undergo post-orchiectomy treatment if they were older, traveled farther to a treatment center, and had a higher disease stage.
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Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/terapia , Adolescente , Criança , Estudos de Coortes , Terapia Combinada , Humanos , Masculino , OrquiectomiaRESUMO
BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3â×â1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.
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Adenoviridae/genética , Vacina BCG/administração & dosagem , Carcinoma in Situ/terapia , Resistencia a Medicamentos Antineoplásicos , Terapia Genética , Vetores Genéticos , Interferon alfa-2/genética , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Idoso , Vacina BCG/efeitos adversos , Carcinoma in Situ/genética , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Progressão da Doença , Feminino , Terapia Genética/efeitos adversos , Terapia Genética/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Background Few in-depth reports on cancer epidemiology in New Mexico or the United States-Mexico border region exist. We aim to quantify cancer incidence and survival in New Mexico and the United States-Mexico border region in New Mexico. Methods Incidence and survival were obtained using SEER*Stat 8.3. The data were divided into either New Mexico, or SEER 18 (comprised of the 17 remaining regions) and then further divided by county in New Mexico and by time period. Incidence rates were age-standardized to the 2000 US census. Five-year survival was calculated for each cancer type. Kaplan-Meier survival plots were produced, and significance was determined using log-rank analysis. Results Analysis demonstrated that cancers in New Mexico are diagnosed at a lower rate with the exception of thyroid, liver, and ovarian. Survival is generally lower in New Mexico with 10 of the 14 cancers having worse survival in New Mexico. Only uterine cancer had improved survival in New Mexico (77.9% vs 74.9%, P < .001). Additionally, breast (82.2%), prostate (83.3%), lung and bronchus (13.7%), colorectal (53.7%), melanoma (80.1%), kidney and renal pelvis (61.2%), uterine (78.5%), and ovarian (41.6%) all had lower survival in the border counties. Conclusion Comparing New Mexico to the other regions in the SEER 18 database, both cancer incidence and survival are consistently lower; these findings could be explained by lower access to healthcare, which can result in underreporting and delays in diagnosis.
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Renal cell carcinoma (RCC) with invasion into the renal vein is well described; however, invasion into the gonadal vein is a rare event with less than five cases reported in the literature. RCC occasionally presents with metastasis to the ovaries or the fallopian tubes, although this is also a rare occurrence. We present a case of locally advanced left RCC with direct extension into the ipsilateral gonadal vein with extension into the bilateral ovaries and uterus, which has not been previously described. Computed tomography (CT) in a 72-year-old female with a 35-pound weight loss indicated the presence of a 16-cm left renal mass with caudal tumor extension through the left gonadal vein and regional lymphadenopathy. There was no evidence of distant metastasis, and she underwent an open left radical nephrectomy. Intraoperatively, she was found to have direct extension of the tumor through the left gonadal vein into the uterus, bilateral ovaries, and the left fallopian tube. All visible disease was resected, and retroperitoneal and pelvic lymphadenectomy were performed. The patient had an uneventful hospital course. Pathology revealed clear cell RCC, Fuhrman grade 3. The final pathologic stage was pT4N1M1. The patient was ultimately noted to have pulmonary metastasis and was treated with immunotherapy with no evidence of disease progression.
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Objective: To examine incidence and survival of testicular cancer in New Mexico, overall and separately for border and non-border counties. Methods: Incidence and 5-year survival rates for testicular cancer were obtained from the SEER18 database using the SEER*Stat program following established NCI protocols. Incidence data were compared using Student's t-test. Age-adjusted 5-year survival and Kaplan-Meier method were used to estimate survival. Log-rank tests were used to compare survival for New Mexico to the remaining17 geographical areas of the SEER 18 and for the New Mexico border counties to the New Mexico non-border counties. Odds ratios were used to compare testicular stage at diagnosis. Cox proportional hazards regression was performed to account for race/ethnicity, and border status. Results: From 2000-2015, New Mexico had a testicular cancer incidence rate of 6.3 per 100,000 people, significantly higher than SEER18 (P<.001). The 5-year survival rate in New Mexico did not differ significantly from the SEER18 (P=.3). Border Hispanics had a lower survival rate than border non-Hispanic populations (P=.03). From 2000-2018, New Mexico had a significantly higher proportion of distant cancers than the SEER18 (OR: 1.29, 95% CI: 1.08 to 1.53, P=.005). Conclusions: The higher incidence of testicular cancer in New Mexico does not appear to have a clear explanation based on the current understanding of risk factors; however, the increased incidence in New Mexico does not appear to be associated with increased mortality. The higher proportion of advanced testicular cancers in New Mexico may represent a delay in diagnosis. The increased mortality rate seen in Hispanic border populations may be due in part to barriers to care.
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Diagnóstico Tardio , Neoplasias Testiculares , Diagnóstico Tardio/prevenção & controle , Diagnóstico Tardio/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , New Mexico/epidemiologia , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Taxa de Sobrevida , Neoplasias Testiculares/etnologia , Neoplasias Testiculares/patologiaRESUMO
PURPOSE: We evaluated health related quality of life following robotic and open radical cystectomy as a treatment for bladder cancer. MATERIALS AND METHODS: Using the Randomized Open versus Robotic Cystectomy (RAZOR) trial population we assessed health related quality of life by using the Functional Assessment of Cancer Therapy (FACT)-Vanderbilt Cystectomy Index and the Short Form 8 Health Survey (SF-8) at baseline, 3 and 6 months postoperatively. The primary objective was to assess the impact of surgical approach on health related quality of life. As an exploratory analysis we assessed the impact of urinary diversion type on health related quality of life. RESULTS: Analyses were performed in subsets of the per-protocol population of 302 patients. There was no statistically significant difference between the mean scores by surgical approach at any time point for any FACT-Vanderbilt Cystectomy Index subscale or composite score (p >0.05). The emotional well-being score increased over time in both surgical arms. Patients in the open arm showed significantly better SF-8 sores in the physical and mental summary scores at 6 months compared to baseline (p <0.05). Continent diversion (versus noncontinent) was associated with worse FACT-bladder-cystectomy score at 3 (p <0.01) but not at 6 months, and the SF-8 physical component was better in continent-diversion patients at 6 months (p=0.019). CONCLUSIONS: Our data suggests lack of significant differences in the health related quality of life in robotic and open cystectomies. As robotic procedures become more widespread it is important to discuss this finding during counseling.
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Cistectomia/métodos , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC. PATIENTS AND METHODS: Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT). RESULTS: Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology. CONCLUSIONS: This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.