RESUMEN
BACKGROUND. Accumulating evidence indicates that hepatocellular adenoma (HCA) may have a higher frequency of hepatobiliary phase (HBP) iso- or hyperintensity than previously reported. OBJECTIVE. The purpose of this study was to evaluate the proportion of HCA that shows iso- or hyperintensity in the HBP of gadoxetic acid-enhanced MRI, stratified by HCA subtype (HNF1a-inactivated [H-HCA], inflammatory [I-HCA], ß-catenin-activated [B-HCA], and unclassified [U-HCA] HCA), and to assess the diagnostic performance of HBP iso- or hyperintensity for differentiating focal nodular hyperplasia (FNH) from HCA. EVIDENCE ACQUISITION. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched through February 14, 2022, for articles reporting HBP signal intensity on gadoxetic acid-enhanced MRI among pathologically proven HCAs, stratified by subtype. The pooled proportion of HBP iso- or hyperintensity was determined for each subtype and compared using metaregression. Diagnostic performance of HBP iso- or hyperintensity for differentiating FNH from all HCA subtypes combined and from B-HCA and U-HCA combined was assessed using bivariate modeling. EVIDENCE SYNTHESIS. Twenty-eight studies (12 original investigations, 16 case reports or case series) were included, yielding 364 patients with 410 HCAs (112 H-HCAs, 203 I-HCAs, 33 B-HCAs, 62 U-HCAs). Pooled proportion of HBP iso- or hyperintensity was 14% (95% CI, 4-26%) among all HCAs, 0% (95% CI, 0-2%) among H-HCAs, 11% (95% CI, 0-29%) among U-HCAs, 14% (95% CI, 2-31%) among I-HCAs, and 59% (95% CI, 26-88%) among B-HCAs; metaregression showed significant difference among subtypes (p < .001). In four studies reporting diagnostic performance information, HBP iso- or hyperintensity had sensitivity of 99% (95% CI, 57-100%) and specificity of 89% (95% CI, 82-94%) for differentiating FNH from all HCA subtypes and sensitivity of 99% (95% CI, 53-100%) and specificity of 65% (95% CI, 44-80%) for differentiating FNH from B-HCA or U-HCA. CONCLUSION. HCA subtypes other than H-HCA show proportions of HBP iso- or hyperintensity ranging from 11% (U-HCA) to 59% (B-HCA). Low prevalence of B-HCA has contributed to prior reports of high diagnostic performance of HBP iso- or hyperintensity for differentiating FNH from HCA. CLINICAL IMPACT. Radiologists should recognize the low specificity of HBP iso- or hyperintensity on gadoxetic acid-enhanced MRI for differentiating FNH from certain HCA subtypes.
Asunto(s)
Adenoma de Células Hepáticas , Hiperplasia Nodular Focal , Neoplasias Hepáticas , Humanos , Adenoma de Células Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Medios de Contraste , Sensibilidad y Especificidad , Gadolinio DTPA , Imagen por Resonancia Magnética , Aminas , Estudios Retrospectivos , Diagnóstico DiferencialRESUMEN
BACKGROUND: Biliary cystic tumours (BCT) [biliary cystadenoma (BCA) and cystadenocarcinoma (BCAC)] warrant complete resection. Simple liver cysts (SLC) require fenestration when symptomatic. Distinguishing between BCT and atypical SLC with pre-operative imaging is not well studied. METHODS: All patients undergoing surgery for a pre-operative suspected SLC or BCT between 1992 and 2014 were included. Peri-operative data were retrospectively reviewed. A blind radiological review of pre-operative imaging was performed. RESULTS: Ninety-four patients underwent fenestration (n = 54) or complete excision (n = 40). Final pathology was SLC (n = 74), BCA (n = 15), BCAC (n = 2) and other primary malignancies (n = 3). A frozen section (FS) was performed in 36 patients, impacting management in 10 (27.8%) by avoiding (n = 1) or mandating a liver resection (n = 9). Frozen section results were always concordant with final pathology. Upon blind review, a solitary lesion, suspicious intracystic component, septation and biliary dilatation were associated with BCT (P < 0.05). Diagnostic sensitivity was high (87.5-100%) but specificity was poor (43.1-53.4%). The diagnostic value of imaging was most accurate when negative for BCT (negative predictive value: 92.5-100%). CONCLUSION: Radiological assessment of hepatic cysts is relatively inaccurate as SLC frequently present with concerning features. In the absence of a strong suspicion of malignancy, fenestration and FS should be considered prior to a complete resection.
Asunto(s)
Quistes/diagnóstico , Diagnóstico por Imagen/métodos , Hepatectomía , Hepatopatías/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Quistes/cirugía , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Hepatopatías/cirugía , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Adulto JovenRESUMEN
PURPOSE: To correlate the MRI features of sclerosed hemangiomas with histologic appearance. MATERIALS AND METHODS: A medical record search identified patients with sclerosed hemangioma who underwent MRI and biopsy/resection from January 2000 to March 2012 for this retrospective institutional review board approved study. Two radiologists independently performed image analysis. A pathologist evaluated lesion histologic characteristics. RESULTS: Twelve patients (median age 65; range 4178 years) were included; 7/12 patients had typical hemangiomas which were also analyzed. Sclerosed hemangiomas were less often moderately T2 hyperintense (5/11 45%; compared with 7/7, 100%; P = 0.0377) and demonstrated moderate arterial phase enhancement less frequently (4/12, 33% compared with 7/7, 100%; P = 0.0128) than typical hemangiomas. Markedly sclerosed hemangiomas (N = 7) exhibited the least "typical" findings, including mild T2 hyperintensity (5/7; 71%), absent arterial phase enhancement (4/7; 57%), mild portal venous phase enhancement (6/7; 86%), and absent centripetal fill-in (6/7; 86%). Arterial phase hyperenhancement occurred more often in mild/moderately sclerosed hemangiomas (3/5; 60%) compared with markedly sclerosed hemangiomas (1/7; 14%). CONCLUSION: Sclerosed hemangiomas exhibit MRI features that appear to correspond with the degree of sclerosis. These features coupled with the presence of other typical hemangiomas may aid in prospectively diagnosing sclerosed hemangioma.
Asunto(s)
Histiocitoma Fibroso Benigno/patología , Neoplasias Hepáticas/patología , Hígado/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Retrospectivos , Estadística como AsuntoRESUMEN
UNLABELLED: What's known on the subject? and what does the study add?: No recent advances have been made in the treatment of patients with advanced bladder cancer and, to date, targeted therapies have not resulted in an improvement in outcome. The mammalian target of rapamycin pathway has been shown to be up-regulated in bladder cancer and represents a rational target for therapeutic intervention. In the present phase II study of everolimus, one near-complete response, one partial response and several minor responses suggest that everolimus possesses biological activity in a subset of patients with bladder cancer. To maximize benefit from targeted agents such as everolimus, the preselection of patients based on molecular phenotype is required. OBJECTIVE: To assess the efficacy and tolerability of everolimus in advanced urothelial carcimoma (UC). PATIENTS AND METHODS: The present study comprised a single-arm, non-randomized study in which all patients received everolimus 10 mg orally once daily continuously (one cycle = 4 weeks). In total, 45 patients with metastatic UC progressing after one to four cytotoxic agents were enrolled between February 2009 and November 2010 at the Memorial Sloan-Kettering Cancer Center. The primary endpoints were 2-month progression-free survival (PFS) and the safety of everolimus, with the secondary endpoint being the response rate. A Simon minimax two-stage design tested the null hypothesis that the true two month PFS rate was ≤ 50%, as opposed to the alternative hypothesis of ≥ 70%. RESULTS: The most common grade 3/4 toxicities were fatigue, infection, anaemia, lymphopaenia, hyperglycaemia and hypophosphataemia. There were two partial responses in nodal metastases, with one patient achieving a 94% decrease in target lesions and remaining on drug at 26 months. An additional 12 patients exhibited minor tumour regression. There were 23 of 45 (51%) patients who were progression-free at 2 months with a median (95% CI) PFS of 2.6 (1.8-3.5) months and a median (95% CI) overall survival of 8.3 (5.5-12.1) months. No clear association was observed between mammalian target of rapamycin pathway marker expression and 2-month PFS. CONCLUSIONS: Although everolimus did not meet its primary endpoint, one partial response, one near-complete response and twelve minor regressions were observed. Everolimus possesses meaningful anti-tumour activity in a subset of patients with advanced UC. Studies aiming to define the genetic basis of everolimus activity in individual responders are ongoing.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Sirolimus/análogos & derivados , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/secundario , Ensayos Clínicos Fase II como Asunto , Everolimus , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sirolimus/uso terapéutico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: Preoperative radiographic differentiation of mucinous cystic neoplasms (MCN) and simple cysts (SLC) of the liver is challenging. Previous data have demonstrated that the finding of septations arising from the cyst wall without indentation on cross-sectional imaging is associated with MCN. We aim to assess whether this radiographic feature is diagnostic of MCN. METHODS: A prospectively maintained database was queried for patients with a preoperative diagnosis of a cystic liver lesion who subsequently underwent operative intervention. The feature of septations without indentation of the cyst wall was evaluated on cross-sectional imaging obtained within 3 months of operation. Imaging was independently evaluated by three radiologists blinded to pathology and interobserver agreement was compared to assess the diagnostic accuracy of this feature as well as the overall likelihood of the lesion representing a MCN. RESULTS: There were 95 patients who met inclusion criteria; 80 (84%) had SLC on pathology, while 15 (16%) had MCN. Presence of septa without indentation of cyst wall had high sensitivity (range 80-87%), but low specificity (range 48-66%). Interobserver percent agreement (PA) was 51% [κ = 0.35 (95% CI 0.22-0.47)]. Sensitivity among the three radiologists ranged between 20 and 80% and specificity between 71 and 91% for the likelihood of the lesion representing MCN versus SLC, with an area under the curve (AUC) of 0.67-0.79; however, interobserver agreement was fair [κ = 0.40 (95% CI 0.25-0.55), PA = 67%]. CONCLUSION: The presence of septations without indentation of cyst wall demonstrates adequate sensitivity to differentiate MCN and SLC. However, there is variability for detection of this feature and therefore, it alone is of limited clinical value.
Asunto(s)
Mucocele , Neoplasias Pancreáticas , Humanos , Hígado/patología , Imagen por Resonancia Magnética/métodos , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: Multiple studies have defined criteria for the selection of thyroid nodules for biopsy. No set of criteria is sufficiently sensitive and specific. The aim of this study is to develop a method for assessing consistency of practice in an ultrasound group and to determine whether a 5-point malignancy rating scale can be used to select patients for biopsy. MATERIALS AND METHODS: One hundred one nodules (50 benign and 51 malignant) were selected from a thyroid biopsy database. Seven radiologists were educated on evidence-based criteria used to select nodules for biopsy. Using this information, readers graded the likelihood of malignancy using a 5-point malignancy rating scale, where 1 equals the lowest probability of malignancy and 5 equals the highest probability of malignancy, on the basis of overall impression of sonographic findings. Interobserver agreement on biopsy recommendation, reader sensitivity, specificity, and accuracy were determined. RESULTS: The sensitivity and specificity of biopsy recommendation were 96.1% and 52%, respectively. The misclassification rate was 25.7%, and accuracy was 74.3%. Interobserver agreement on biopsy recommendation was fair to substantial (κ, 0.38-0.69). The proportion of agreement was excellent for malignant nodules (0.88-1.0). The risk of malignancy increased with increasing malignancy rating: 4.3% of nodules with a malignancy rating of 1 were malignant versus 93.4% of those assigned a rating of 5. CONCLUSION: Our study illustrates a method to evaluate the standard of practice for thyroid nodule assessment among radiologists within an ultrasound group. Application of a 5-point malignancy rating scale to select nodules for biopsy is feasible and shows good diagnostic accuracy.
Asunto(s)
Biopsia/normas , Medicina Basada en la Evidencia , Guías de Práctica Clínica como Asunto , Nódulo Tiroideo/patología , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Curva ROC , Sensibilidad y Especificidad , Nódulo Tiroideo/diagnóstico por imagen , UltrasonografíaRESUMEN
PURPOSE: To evaluate the associations between computed tomography (CT) imaging features extracted from the structured American Pancreatic Association (APA)/Society of Abdominal Radiology (SAR) template and overall survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective analysis included consecutive patients with PDAC who consented to genomic tumor testing and underwent preoperative imaging and curative intent surgical resection from December 2006 to July 2017. Two radiologists assessed preoperative CT imaging using the APA/SAR PDAC-reporting template. Univariable associations between overall survival and imaging variables were evaluated using Cox proportional hazards regression. RESULTS: The study included 168 patients (66 years ± 11; 91 women). 126/168 patients (75%) received upfront surgical resection whereas 42/168 (25%) received neoadjuvant therapy prior to surgical resection. In the entire cohort, features associated with decreased overall survival were tumor arterial contact of any kind (hazard ratio (HR) 1.89, 95% CI 1.13-3.14, p = 0.020), tumor contact with the common hepatic artery (HR 2.33, 95% CI 1.35-4.04, p = 0.009), and portal vein deformity (HR 3.22, 95% CI 1.63-6.37, p = 0.003). In the upfront surgical group, larger tumor size was associated with decreased overall survival (HR 2.30, 95% CI 1.19-4.42, p = 0.013). In the neoadjuvant therapy group, the presence of venous collaterals was the only feature associated with decreased overall survival (HR 2.28, 95% CI 1.04-4.99, p = 0.042). CONCLUSION: The application of the APA/SAR pancreatic adenocarcinoma reporting template may identify predictors of survival that can aid in preoperative stratification of patients.
Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Femenino , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To determine the incremental benefit of combined endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging, as compared with endorectal MR imaging alone, for sextant localization of peripheral zone (PZ) prostate cancer. MATERIALS AND METHODS: This prospective multicenter study, conducted by the American College of Radiology Imaging Network (ACRIN) from February 2004 to June 2005, was institutional review board approved and HIPAA compliant. Research associates were required to follow consent guidelines approved by the Office for Human Research Protection and established by the institutional review boards. One hundred thirty-four patients with biopsy-proved prostate adenocarcinoma and scheduled to undergo radical prostatectomy were recruited at seven institutions. T1-weighted, T2-weighted, and spectroscopic MR sequences were performed at 1.5 T by using a pelvic phased-array coil in combination with an endorectal coil. Eight readers independently rated the likelihood of the presence of PZ cancer in each sextant by using a five-point scale-first on MR images alone and later on combined MR-MR spectroscopic images. Areas under the receiver operating characteristic curve (AUCs) were calculated with sextant as the unit of analysis. The presence or absence of cancer at centralized histopathologic evaluation of prostate specimens was the reference standard. Reader-specific receiver operating characteristic curves for values obtained with MR imaging alone and with combined MR imaging-MR spectroscopic imaging were developed. The AUCs were estimated by using Mann-Whitney statistics and appropriate 95% confidence intervals. RESULTS: Complete data were available for 110 patients (mean age, 58 years; range, 45-72 years). MR imaging alone and combined MR imaging-MR spectroscopic imaging had similar accuracy in PZ cancer localization (AUC, 0.60 vs 0.58, respectively; P > .05). AUCs for individual readers were 0.57-0.63 for MR imaging alone and 0.54-0.61 for combined MR imaging-MR spectroscopic imaging. CONCLUSION: In patients who undergo radical prostatectomy, the accuracy of combined 1.5-T endorectal MR imaging-MR spectroscopic imaging for sextant localization of PZ prostate cancer is equal to that of MR imaging alone.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Prostatectomía , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estados UnidosRESUMEN
OBJECTIVE: The purpose of our study is to present the radiographic findings in a series of 16 patients with complications associated with intravesical bacille Calmette-Guérin (BCG) treatment of bladder cancer. CONCLUSION: Intravesical BCG-related complications such as granulomatous disease may show imaging findings mimicking primary or metastatic tumors in patients with bladder cancer. Radiologists should consider this possibility when imaging abnormalities are encountered in bladder cancer patients treated with intravesical BCG so that appropriate management can be administered and unnecessary procedures avoided.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/uso terapéutico , Diagnóstico por Imagen/métodos , Granuloma/diagnóstico , Granuloma/etiología , Administración Intravesical , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Enfermedades de la Vejiga UrinariaRESUMEN
OBJECTIVE: Determine the safety and efficacy of cetuximab plus paclitaxel and carboplatin as initial treatment of stage III/IV ovarian cancer. METHODS: An initial intravenous [IV] dose of cetuximab (400 mg/m(2)) was administered over 120 min followed by weekly IV infusions of cetuximab (250 mg/m(2)) administered over 60 min. Paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] of 6) were administered IV every 21 days for 6 cycles. The order of administration was cetuximab followed by paclitaxel and then carboplatin. Patients achieving a clinical complete response after 6 cycles were eligible to continue weekly cetuximab for 6 months or until toxicity or disease progression. Safety was evaluated using NCI Common Toxicity Criteria version 2.0. Progression-free survival (PFS) at 18 months was determined and compared with historical controls. RESULTS: Forty-one patients were enrolled in this study; 40 received treatment and were evaluable for toxicity, and 38 were evaluable for PFS. Grade 3/4 treatment-related toxicities included febrile neutropenia (12.5%), rash (2.5%), hypersensitivity reaction (7.5%), and hypomagnesemia (12.5%). Common grade 1/2 toxicities attributed to cetuximab included acneiform rash (82.5%), hirsutism (7.5%) or abnormal hair growth (25%), and nail disorders (22.5%), which in 3 cases resulted in the patient's discontinuation from the study. Median PFS was 14.4 months, and PFS at 18 months was 38.8%. CONCLUSIONS: The combination of cetuximab with paclitaxel and carboplatin is adequately tolerated as primary therapy for ovarian cancer but did not demonstrate prolongation of PFS when compared to historical data.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Cetuximab , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Neoplasias de las Trompas Uterinas/patología , Neoplasias de las Trompas Uterinas/cirugía , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/cirugíaRESUMEN
BACKGROUND: Cisplatin-based combination chemotherapy is standard first-line treatment for patients with advanced urothelial carcinoma (UC). Molecular profiling studies reveal that the PI3K/AKT/mTOR pathway is altered in a significant percentage of UCs. OBJECTIVE: We conducted a phase I trial to evaluate the feasibility of combining the mTOR inhibitor everolimus with gemcitabine and split-dose cisplatin (GC) in advanced UC in the first-line setting. METHODS: Patients received gemcitabine 800âmg/m2 and cisplatin 35âmg/m2 on days 1 and 8 of 21-day cycles for a total of 6 cycles in combination with everolimus at increasing dose levels (DL1:5âmg QOD, DL2:5âmg daily, DL3:10âmg daily) following a standard 3+3 design. Responses were assessed every 2 cycles. Patients with at least stable disease (SD) continued everolimus until progression. Goals were to establish dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for the combination. RESULTS: 12 patients were enrolled, 3 at DL1, 3 at DL2, and an additional 6 at DL1 *(DL1 following de-escalation). 3/3 patients at DL2 had DLTs during cycle 1. 2/8 evaluable patients at DL1/DL1 * had DLTs during cycle 1. DLTs were primarily hematologic. Further toxicities, also primarily hematologic, were observed during later treatment cycles, leading to 8 chemotherapy dose reductions overall. Partial responses were observed in 4/10 evaluable patients, and SD in 5/10. Median overall survival was 10.8 months (95% CI 6.9, not reached). CONCLUSIONS: The maximum tolerated dose was reached at the lowest dose level, 5âmg QOD, for everolimus in combination with gemcitabine and split-dose cisplatin in advanced UC. The regimen was limited by hematologic toxicity.
RESUMEN
PURPOSE: Intraperitoneal (IP) cisplatin and intravenous (IV) or IP paclitaxel constitute a standard therapy for optimally debulked ovarian cancer. Bevacizumab prolongs progression-free survival (PFS) when included in first-line IV chemotherapy. In this study, the safety and feasibility of adding bevacizumab to a first-line IP regimen were assessed. PATIENTS AND METHODS: Treatment was as follows: paclitaxel 135 mg/m(2) IV over 3 hours day 1, cisplatin 75 mg/m(2) IP day 2, and paclitaxel 60 mg/m(2) IP day 8. Bevacizumab 15 mg/kg IV was given after paclitaxel on day 1 beginning in cycle 2. After six cycles of chemotherapy, bevacizumab was given every 3 weeks for 17 additional treatments. The primary end point was safety and tolerability determined by whether 60% of patients completed six cycles of IV/IP chemotherapy. RESULTS: Of 41 treated patients, 30 (73%) received six cycles of IV/IP chemotherapy and 35 (85%) received at least four cycles. Three (27%) of those who discontinued chemotherapy did so because of complications related to bevacizumab (hypertension, n = 2; perforation, n = 1). Grades 3 to 4 toxicities included neutropenia (34%), vasovagal syncope (10%), hypertension (7%), nausea/vomiting (7%), hypomagnesemia (7%), and abdominal pain (7%). There were three grade 3 small bowel obstructions (7%) during cycles 3, 9, and 15. One patient died following rectosigmoid anastomotic dehiscence during cycle 4. Estimated median PFS is 28.6 months (95% CI, 19.1 to 38.9 months). Three patients (7%) had IP port malfunction. CONCLUSION: The addition of bevacizumab to this IP regimen is feasible; however, bevacizumab may increase the risk of bowel obstruction/perforation. The observed median PFS is similar to that seen with IP/IV chemotherapy alone.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Carcinoma Epitelial de Ovario , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Parenterales , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Proyectos PilotoRESUMEN
BACKGROUND: Sunitinib has activity in patients with metastatic urothelial cancer (UC), but most patients do not respond. OBJECTIVE: To identify predictors of response to sunitinib. DESIGN, SETTING, AND PARTICIPANTS: Seventy-seven patients with advanced UC received sunitinib on one of two schedules at a single institution. Blood pressure (BP), immunohistochemistry (IHC), and pharmacokinetic (PK) results were correlated with response to sunitinib. MEASUREMENTS: BP was assessed on day 1 and 28 of each cycle and on day 14 of cycle 1. IHC was performed on 55 samples from 38 cases using mammalian target of rapamycin and hypoxia-inducible factor (HIF) pathway marker antibodies. Blood samples for PK analysis were collected from 15 patients at three time points. Response was assessed using Response Evaluation Criteria in Solid Tumors criteria. RESULTS AND LIMITATIONS: Sunitinib-induced hypertension predicted improved response when hypertension was categorized as a discrete (p = 0.02) or continuous variable (p = 0.005 [systolic BP] and p = 0.007 [diastolic BP]). The odds ratio of response was 12.5 (95% confidence interval, 1.95-246.8) for grade 3/4 hypertension compared with grade 0. Response was associated with low HIF-1α expression in primary (p = 0.07) tissue. A nonstatistically significant trend was seen for an association between greater drug concentration and best response. A correlation between expression markers within the same pathways was identified, phosphorylated-4EBP1 and phosphorylated-S6 (p = 6.5 × 10(-9)), and vascular endothelial growth factor receptor 2 and HIF-1α (p = 0.008). Results are limited by small numbers. CONCLUSIONS: Clinical and molecular biomarkers of response to sunitinib may have clinical relevance and require prospective validation. There is an urgent need for predictive biomarkers to guide the management of UC.
Asunto(s)
Inhibidores de la Angiogénesis/farmacocinética , Biomarcadores de Tumor/antagonistas & inhibidores , Carcinoma de Células Transicionales/tratamiento farmacológico , Inmunohistoquímica , Indoles/farmacocinética , Pirroles/farmacocinética , Neoplasias Urológicas/tratamiento farmacológico , Urotelio/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/análisis , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Biomarcadores de Tumor/análisis , Presión Sanguínea/efectos de los fármacos , Carcinoma de Células Transicionales/química , Carcinoma de Células Transicionales/patología , Proteínas de Ciclo Celular , Esquema de Medicación , Humanos , Hipertensión/inducido químicamente , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Indoles/administración & dosificación , Indoles/efectos adversos , Modelos Logísticos , Ciudad de Nueva York , Fosfoproteínas/análisis , Fosforilación , Pirroles/administración & dosificación , Pirroles/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sunitinib , Serina-Treonina Quinasas TOR/análisis , Análisis de Matrices Tisulares , Resultado del Tratamiento , Neoplasias Urológicas/química , Neoplasias Urológicas/patología , Urotelio/química , Urotelio/patología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisisRESUMEN
PURPOSE: No standard therapy exists for metastatic urothelial cancer (UC) that has progressed after initial chemotherapy. This trial was designed to assess the efficacy and tolerability of sunitinib in patients with advanced, previously treated UC. PATIENTS AND METHODS: In this phase II trial, 77 patients received sunitinib between September 2006 and January 2009 on one of two schedules (50 mg per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously [cohort B]), using a Simon 2 stage design in each cohort separately. RESULTS: A partial response was seen in three of 45 patients (95% CI, 1% to 18%) in cohort A, and in one of 32 patients (95% CI, 0% to 16%) in cohort B. Clinical regression or stable disease was achieved in 33 of 77 patients (43%). Tumor regression lasted between 0.6 and 23.4 months with 29% of patients achieving response lasting longer than 3 months. The progression-free survival (2.4 v 2.3 months; P = .4) and overall survival (7.1 v 6.0 months; P = .4) were similar in both cohorts. There was one treatment-related death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3 or 4 toxicity. CONCLUSION: Sunitinib did not achieve the predetermined threshold of >or= 20% activity defined by Response Evaluation Criteria in Solid Tumors. However, antitumor responses were observed, identifying the vascular endothelial growth factor axis as a viable pathway for UC treatment. The reported clinical benefit in previously treated patients warrants further investigation in a disease for which there is no US Food and Drug Administration-approved treatment.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Indoles/uso terapéutico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Pirroles/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Indoles/efectos adversos , Indoles/farmacología , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/secundario , Pirroles/efectos adversos , Pirroles/farmacología , Sunitinib , Análisis de Supervivencia , Urotelio/patologíaRESUMEN
BACKGROUND: A 59-year-old man on exogenous androgen therapy presented with a clinically palpable prostate nodule confined to one lobe on endorectal examination. Serum prostate-specific antigen was 3.4 ng/ml. Bone scintigraphy and baseline CT were reportedly negative. INVESTIGATIONS: Physical examination, laboratory evaluation, endorectal MRI of the prostate, cystoscopy and biopsy. DIAGNOSIS: Poorly differentiated adenocarcinoma of the prostate, with invasion of the urinary bladder. MANAGEMENT: Neoadjuvant hormonal therapy, followed by radiation.