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BACKGROUND: The purpose of this study is to assess the body composition changes in men with recently diagnosed oligometastatic prostate cancer following neoadjuvant chemohormonal therapy. Further, we evaluated whether CT-based body composition parameters are associated with biochemical recurrence or imaging progression. MATERIAL AND METHODS: Recently diagnosed castration-naïve oligometastatic prostate cancer patients who received neoadjuvant docetaxel chemotherapy and androgen deprivation treatment (ADT) before prostatectomy and consolidation of local and oligometastatic disease (total eradication therapy), as part of a phase-II prospective clinical trial were included. Body composition parameters including cross-sectional areas of the psoas muscle, total, visceral, and subcutaneous adipose tissue were measured on serial CT scans obtained before and following completion of neoadjuvant treatment. RESULTS: A total of 22 prostate cancer patients were included (median age 58 years, median Gleason score 8). The median time intervals between commencement of neoadjuvant chemohormonal therapy and first and second follow-up CTs were 3 and 12 months, respectively. Compared to the baseline scan, there were significant declines in psoas muscle cross-sectional areas with estimated percentage declines of -13.9% (IQR: 7.6%-16.5%, p < .001) and -13.2% (IQR: 6%-11.2%, p < .001) on first and second follow-up CTs. There were significant increases in subcutaneous adipose tissue following neoadjuvant chemohormonal therapy with percentage increases of +8.9% (IQR: 5.1%-21.5%, p = .002) and +18.9% (IQR: 6.1%-33.8%, p < .001), respectively. The median follow-up was 34.5 months. The estimated 2-year prostate-specific antigen progression-free and radiologic progression-free survival were 95.5%. No significant association between baseline or percentage change in body composition parameters and disease progression were identified. CONCLUSIONS: Our findings showed a significant reduction in muscle mass and an increase in subcutaneous adiposity in men treated with neoadjuvant docetaxel and ADT, more pronounced on the first follow-up scan after completion of neoadjuvant treatment. Body composition parameters were not found to be significant predictors of disease progression in our cohort.
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Composición Corporal , Metástasis de la Neoplasia/fisiopatología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/fisiopatología , Tomografía Computarizada por Rayos X , Anciano , Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos/uso terapéutico , Progresión de la Enfermedad , Docetaxel/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/terapia , Estudios Prospectivos , Prostatectomía , Neoplasias de la Próstata Resistentes a la Castración/patología , Músculos Psoas/diagnóstico por imagen , Grasa Subcutánea/diagnóstico por imagenRESUMEN
PURPOSE: To determine the efficacy of combined continuous sorafenib therapy and drug-eluting bead (DEB) transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was conducted in accordance with the principles of the Declaration of Helsinki, and all patients provided written informed consent prior to enrollment. Inclusion criteria included unresectable HCC, a treatment naïve status, an Eastern Cooperative Oncology Group score of 0-1, and a Child-Pugh score of A-B7. Continuous sorafenib therapy (400 mg twice daily) was started 1 week before the first round of DEB TACE, which was performed in 6-week cycles. Up to four rounds of DEB TACE therapy were allowed on demand within 6 months. The primary end point was safety. Secondary end points were time to progression (TTP), response rate, and overall survival (OS) and were stratified by the Barcelona Clinic Liver Cancer (BCLC) stage and the duration of sorafenib therapy. OS was assessed with Kaplan-Meier estimates, and the Mantel-Cox log-rank test was used to determine differences in survival. A two-sided P value of less than .05 was considered to indicate a significant difference. The study was approved by the Johns Hopkins institutional review board and remained open from March 2009 to January 2012. RESULTS: Fifty patients--of whom 76% were male, 92% had a Child-Pugh score of A, and 62% had BCLC stage C disease--underwent a median of three cycles of therapy. The 6-month disease control rate (defined as complete response plus partial response plus stable disease) was 94% according to the response evaluation criteria in solid tumors. Median TTP and OS were 13.9 and 20.4 months, respectively, and 81% of toxicities were grades 1-2. There was one death that was possibly treatment related. CONCLUSION: Combined continuous sorafenib therapy and on-demand DEB TACE provided excellent local disease control and did not lead to multiplicative toxicities. Long-term administration of sorafenib therapy in combination with DEB TACE may have a survival benefit in patients with advanced HCC.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Carcinoma Hepatocelular/patología , Medios de Contraste , Quimioterapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Niacinamida/uso terapéutico , Sorafenib , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To investigate the feasibility that arterial enhancement fraction (AEF) is associated with response of hepatocellular carcinoma (HCC) following intra-arterial therapy (IAT) and to compare AEF response with currently used tumor response metrics. MATERIALS AND METHODS: The AEF, Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) of the largest treated index lesion and AEF of the tumor-free hepatic parenchyma was measured on representative axial images in 131 patients (108 male; mean age, 61.9 years). Clinical measures and patient survival were assessed. Statistical analysis included Wilcoxon signed-rank test and the COX proportional hazards model. RESULTS: After IAT, the mean AEF of the tumor decreased by 22% (66.7-44.8%, P < 0.0001), while the mean AEF of the tumor-free parenchyma remained unchanged (27.2-26.5%, P = 0.50). Median survival of all 131 patients with liver cancer was 17 months. Patients were stratified into AEF-responders if they had an AEF-decrease ≥35% (AEF-responders: n = 67; AEF-nonresponders: n = 64). AEF-responders survived longer than nonresponders (34.8 months versus 10.8 months, hazard ratio = 0.39; P < 0.0001). Responders according to RECIST, mRECIST, or EASL did not survive significantly longer compared with nonresponders. CONCLUSION: Evaluating the AEF values based on tri-phasic MRI is associated with tumor response in patients with unresectable HCC treated with IAT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador , Infusiones Intraarteriales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Imagen por Resonancia Magnética/métodos , Anciano , Carcinoma Hepatocelular/irrigación sanguínea , Femenino , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas/irrigación sanguínea , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Vascular endothelial growth factor is up-regulated in hepatocellular carcinoma (HCC) and is further up-regulated after transhepatic arterial chemoembolization. The authors of this report conducted a phase 2 trial to evaluate the safety and efficacy of bevacizumab combined with chemoembolization in patients with unresectable HCC. METHODS: Patients who had an Eastern Cooperative Oncology Group performance of status 0 to 2, a Child-Pugh score of A or B, and Barcelona Clinic Liver Cancer stage B or C HCC were eligible. Treatment consisted of bevacizumab every 2 weeks and chemoembolization during the third week of a 6-week cycle for up to 3 cycles over 6 months. The primary endpoints were safety and efficacy. RESULTS: Twenty-five patients received chemoembolization and bevacizumab. The most common grade 3 and 4 events after the first treatment cycle were leukocytopenia (12%), fatigue (12%), and hyponatremia (12%). Serious toxicities that had a known association with bevacizumab were observed in 4 patients. Thirty-day mortality was 0%. The median time to tumor progression for the targeted lesions was not reached, and overall survival was 10.8 months. The objective response rate was 60% using enhancement response evaluation criteria, and the disease control rate was 100%. CONCLUSIONS: Concurrent treatment with bevacizumab and chemoembolization was safe in carefully selected patients and demonstrated antitumor activity in patients with unresectable HCC. These results support the further development of bevacizumab combined with chemoembolization as a treatment for unresectable HCC.
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Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Bevacizumab , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To show that hepatic tumor volume and enhancement pattern measurements can be obtained in a time-efficient and reproducible manner on a voxel-by-voxel basis to provide a true three-dimensional (3D) volumetric assessment. MATERIALS AND METHODS: Magnetic resonance (MR) imaging data obtained from 20 patients recruited for a single-institution prospective study were retrospectively evaluated. All patients had a diagnosis of hepatocellular carcinoma (HCC) and underwent drug-eluting beads (DEB) transcatheter arterial chemoembolization for the first time. All patients had undergone contrast-enhanced MR imaging before and after DEB transcatheter arterial chemoembolization; poor image quality excluded 3 patients, resulting in a final count of 17 patients. Volumetric RECIST (vRECIST) and quantitative EASL (qEASL) were measured, and segmentation and processing times were recorded. RESULTS: There were 34 scans analyzed. The time for semiautomatic segmentation was 65 seconds±33 (range, 40-200 seconds). vRECIST and qEASL of each tumor were computed<1 minute for each. CONCLUSIONS: Semiautomatic quantitative tumor enhancement (qEASL) and volume (vRECIST) assessment is feasible in a workflow-efficient time frame. Clinical correlation is necessary, but vRECIST and qEASL could become part of the assessment of intraarterial therapy for interventional radiologists.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Reconocimiento de Normas Patrones Automatizadas/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Programas Informáticos , Validación de Programas de Computación , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacosRESUMEN
The application of circulating tumor cells (CTCs) in both clinical practice and research has been continuously limited by the rare number of targets that can be found in a tube of peripheral blood. Diagnostic leukapheresis (DLA) was used to increase the sampling volume. AdnaTest was used to process the whole leukopak, and the RNAs of captured CTCs was then profiled by NanoString nCounter platform. Spike-in experiments and leukopaks from patients with metastatic prostate cancer were used to validate this new strategy. The whole leukopak was further concentrated five times to reduce the total volume from 150 âmL to 30 âmL, which enabled it to be processed by 3 separate AdnaTest kits. The spike-in experiment demonstrated a reliable capture when there were more than 100 cancer cells/10 âmL of concentrated leukopak. In 1 out of 5 real patient samples, CTCs were only detected in the leukopak, but not in peripheral blood. The RNA profiling of DLA CTCs indicated a more aggressive phenotype of CTCs occurred when the patient was experiencing a disease relapse, even when the serum prostate specific antigen (PSA) level was still relatively low and CTCs in peripheral blood were not detectable. We established a new protocol, integrating DLA, AdnaTest and NanoString nCounter technology, to profile RNAs from CTCs captured from a large blood screening volume. The new protocol can process the whole leukopak with sensitive CTC capture. The RNA profiling of CTCs can provide valuable information for disease monitoring.
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Multimodal therapies were combined to eradicate the primary site, metastatic, and micrometastatic disease in men with newly diagnosed, synchronous, oligometastatic prostate cancer. The investigation included companion, phase II studies: total eradication therapy-1 (TET-1) for those treatment-naïve and total eradication therapy-2 (TET-2) for those post-prostatectomy. The treatment-naive protocol included androgen deprivation and docetaxel (with concurrent abiraterone added in a protocol amendment), followed by a prostatectomy, adjuvant radiation (if positive margins, T3/4, or detectable PSA), and metastasis-directed therapy. The post-prostatectomy protocol assigned the same therapies (omitting the prostatectomy). The primary endpoint was an undetectable PSA with recovered testosterone. The safety boundaries were ≤ 50% for grade 3/4 neutropenic and ≤ 20% for grade 3/4 surgical- and radiation-related toxicities. Enrollment was planned for 60 patients per protocol, to detect a PSA progression-free survival ≥ 32%, as compared to 15% in a historic control. Enrollment closed early. An interim analysis was conducted once > 50% of patients were evaluable for the primary endpoint. The primary endpoint duration was assessed by median progression-free survival. 52 patients were enrolled (n = 26 per protocol). Medium follow-up was 30.3 months. 80% (24/30) of evaluable patients achieved the primary endpoint; the duration was not reached. Of those not evaluable, 77% (17/22) had not reached the endpoint and 23% (5/22) had exited. There were 8% (4/52) grade 3/4 neutropenic and 2% (1/48) grade 3/4 surgical or radiation-induced toxicities. Interim findings suggest the trials' endpoints were met, advancing the concept of total eradication therapy in men with oligometastatic prostate cancer.
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Neoplasias de la Próstata , Antagonistas de Andrógenos/uso terapéutico , Humanos , Masculino , Estudios Prospectivos , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/patologíaRESUMEN
The aim of this study was to discuss the appearance of common complications from loco-regional therapy of primary and secondary malignant liver neoplasms on cross-sectional imaging. Knowledge of common complications is important for the safe performance of loco-regional therapy (LRT) and for the interpretation of post-LRT follow-up imaging. With careful patient selection, LRT represents an effective and safe treatment of primary and secondary hepatic malignancies; however, complications related to LRT methods infrequently lead to additional morbidity.
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Antineoplásicos/efectos adversos , Sistemas de Liberación de Medicamentos/efectos adversos , Embolia/complicaciones , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Anciano , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Diagnóstico por Imagen , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
The aim of the study was to evaluate the feasibility of utilizing peripheral androgen blockade in men with biochemical recurrent castrate-sensitive prostate cancer. A registration study to track outcomes of men with biochemical recurrent castrate-sensitive prostate cancer treated with peripheral androgen blockade utilizing concomitant administration of finasteride and bicalutamide. Men were on intermittent peripheral blockade for a median 20.2 months, continuous peripheral blockade for a median 6.8 months, intermittent triple dose peripheral androgen blockade for a median 10.7 months, and continuous triple dose peripheral androgen blockade for 4.4 months before failing therapy. Six men (21%) had additional therapies during treatment that included metastasis-directed therapy (5/37, 14%), systemic Lu-177 (2/37, 5%), and salvage RT (1/37, 3%). The median time to progression, which includes time from initiation through all therapies to the initiation of ADT, was 37.6 months (IQR 20-74.7). From the start of PAB, median time to castrate resistance was 49.8 months (IQR 40.9-NR). After starting ADT, median time to castrate resistance was 8.8 months (IQR 4.6-17.7). Our data support the exploration of PAB as a treatment option in carefully selected patients who present with biochemical recurrence after failure of definitive local therapy for prostate cancer.
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Antagonistas de Andrógenos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Anciano , Andrógenos/metabolismo , Anilidas/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Finasterida/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Nitrilos/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Compuestos de Tosilo/administración & dosificaciónRESUMEN
Bone metastases in prostate cancer (PCa) have important prognostic significance, and imaging modalities used for PCa staging should have high sensitivity for detecting such lesions. Prostate-specific membrane antigen (PSMA)-targeted PET radiotracers are promising new agents for imaging PCa. We undertook a head-to-head comparison of PSMA-targeted 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET to Na18F PET to determine which modality was more sensitive for the detection of lesions suggestive of bone metastases in a group of patients with metastatic PCa. Methods: Patients with progressive, metastatic PCa were prospectively imaged with both 18F-DCFPyL and Na18F PET/CT, with both scans occurring within 24 h of each other. A consensus 2-reader central review was performed to identify all bone lesions suggestive of sites of PCa involvement on both scans, and maximized SUVs corrected for body weight (SUVmax) and lean body mass (SULmax) were recorded. Soft-tissue lesions were also noted on both scans, and SUVmax, SULmax, and PSMA reporting and data system (RADS) version 1.0 scores were recorded. Data from the 2 scans were compared using a generalized estimating equation. Results: In total, 16 patients meeting all inclusion criteria were enrolled in this study, and 15 of the 16 (93.8%) were imaged with both PET radiotracers. In total, 405 bone lesions suggestive of sites of PCa were identified on at least 1 scan. On 18F-DCFPyL PET/CT, 391 (96.5%) were definitively positive, 4 (1.0%) were equivocally positive, and 10 (2.5%) were negative. On Na18F PET/CT, the corresponding values were 388 (95.8%), 4 (1.0%), and 13 (3.2%). Of the definitively negative lesions on 18F-DCFPyL PET, 8 of 10 (80.0%) were sclerotic and 2 of 10 (20.0%) were infiltrative or marrow-based. Additionally, 12 of 13 (92.3%) of the definitively negative lesions on Na18F PET were infiltrative or marrow-based and 1 of 13 (7.7%) was lytic. Also identified were 78 PSMA-RADS-4, 17 PSMA-RADS-5, and 1 PSMA-RADS-3C soft-tissue lesions. Conclusion: PET/CT imaging using 18F-DCFPyL and Na18F PET had nearly identical sensitivities for the detection of bone lesions in patients with metastatic PCa. As would be expected, PSMA-targeted PET provides more information on soft-tissue disease. There may be little additional value to imaging PCa patients with Na18F after a PSMA-targeted PET scan has already been performed.
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Antígenos de Superficie/metabolismo , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Glutamato Carboxipeptidasa II/metabolismo , Lisina/análogos & derivados , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/patología , Fluoruro de Sodio , Urea/análogos & derivados , Radioisótopos de Flúor , Humanos , Masculino , Estudios ProspectivosRESUMEN
PURPOSE: To prospectively assess serial changes in contrast material-enhanced and diffusion-weighted (DW) magnetic resonance (MR) imaging values within 1 month after transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval was obtained for this prospective HIPAA-compliant study. MR imaging was performed before and within 24 hours after TACE in 24 patients with HCC (21 male, three female; mean age, 59 years and 62 years, respectively). Serial MR imaging was subsequently performed 1, 2, 3, and 4 weeks after therapy. The imaging protocol included fast spin-echo T2-weighted MR imaging, breath-hold DW echo-planar MR imaging, and breath-hold unenhanced and contrast-enhanced T1-weighted three-dimensional fat-suppressed gradient-recalled-echo MR imaging in the arterial and portal venous phases. Tumor size, enhancement, and apparent diffusion coefficient (ADC) values were recorded before and sequentially after treatment. Regression models for the correlated data were used to assess changes in these parameters over time after TACE. RESULTS: Mean tumor size was 7.5 cm and was unchanged up to 4 weeks after therapy. Reduction in tumor enhancement in the arterial phase occurred immediately after TACE, with a consistent reduction occurring 1-3 weeks after therapy (P = .001). Reduction in tumor enhancement in the portal venous phase also occurred immediately after TACE, with a consistent reduction occurring 1-3 weeks after therapy (P = .0003). The increase in tumor ADC value was significant 1-2 weeks after therapy (P = .004), borderline significant 3 weeks after therapy, and insignificant 24 hours and 4 weeks after therapy. CONCLUSION: Significant reduction in tumor enhancement occurred within 24 hours after TACE and persisted up to 4 weeks after TACE. Lesser changes in the ADC value appeared 1 week after TACE, persisted through 2 weeks after TACE, and became less apparent 3 and 4 weeks after TACE. No change in tumor size was recorded during the follow-up period.
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Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética/métodos , Medios de Contraste , Femenino , Gadolinio , Humanos , Hígado/irrigación sanguínea , Hígado/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Resultado del TratamientoRESUMEN
PURPOSE: To compare transarterial chemoembolization (CE) versus yttrium-90 ((90)Y) radioembolization (RE) for liver-dominant metastatic colorectal adenocarcinoma as salvage therapy. MATERIALS AND METHODS: Of 36 patients, 21 underwent CE (37 procedures; 11 men; mean age, 67 years; 16 with Child-Pugh class A disease) and 15 underwent (90)Y RE (19 procedures; 11 men; mean age, 64 years; 13 with Child-Pugh class A disease) for liver-dominant colorectal adenocarcinoma. Mean index dominant lesion sizes were 9.3 cm and 8.2 cm in the CE and RE groups, respectively. Multilobar disease was seen in 67% and 87% of the respective groups, and extrahepatic metastases were seen in 43% and 33%, respectively. Mean times from diagnosis of liver metastasis to CE or RE were 17.6 months and 22.6 months, respectively. RESULTS: A total of 37 CE procedures with cisplatin, doxorubicin, and mitomycin were performed, and 19 RE procedures with (90)Y were performed; 43% of patients in the CE group and 20% in the RE group received multiple treatment sessions, and 100% of procedures were technically successful. Median survival times were 7.7 months for the CE group and 6.9 months for the RE group (P = .27). The 1-, 2-, and 5-year survival rates were 43%, 10%, and 0%, respectively, in the CE group; and 34%, 18%, and 0%, respectively, in the RE group. There was one major complication (2.7%) in the CE group (pulmonary embolism), with a 30-day mortality rate of 5.4% (n = 2). There were no major complications in the RE group, with a 30-day mortality rate of 5.2% (n = 1). CONCLUSIONS: Patients with unresectable liver colorectal metastases that progress despite systemic chemotherapy can undergo palliative treatment with CE or RE with similar survival benefit.
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Adenocarcinoma/secundario , Adenocarcinoma/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Colorrectales/terapia , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos/uso terapéutico , Resultado del TratamientoRESUMEN
We present the case of a man with oligometastatic prostate cancer who underwent a PSMA-targeted 18F-DCFPyL PET/CT scan in order to illustrate how the PSMA-RADS grading sytem can be successfully used to support clinical decision-making and treatment planning. Notably, the presented patient was found to have an equivocal bone lesion (PSMA-RADS-3B) which was further worked up with a tumor protocol MRI and found to be definitively benign (PSMA-RADS-1B) and thus removed from the oligometastatic treatment plan. Remaining avid lesions were incorporated into the treatment plan or deferred for later work-up or monitoring, as indicated within the PSMA-RADS framework.
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The bone marrow microenvironment represents a "metastatic niche" in which prostate cancer cells may persist and evade cytotoxic therapy. In order to study the biology of prostate cancer dissemination, we have established a safe and efficient method for performing pubic bone marrow aspiration at the time of radical prostatectomy. We herein describe our experience with this technique.
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PURPOSE: Radioembolization with yttrium-90 microspheres may be optimized with patient-specific pretherapy treatment planning. Dose verification and validation of treatment planning methods require quantitative imaging of the post-therapy distribution of yttrium-90 (Y-90). Methods for quantitative imaging of Y-90 using both bremsstrahlung SPECT and PET have previously been described. The purpose of this study was to compare the two modalities quantitatively in humans. METHODS: Calibration correction factors for both quantitative Y-90 bremsstrahlung SPECT and a non-time-of-flight PET system without compensation for prompt coincidences were developed by imaging three phantoms. The consistency of these calibration correction factors for the different phantoms was evaluated. Post-therapy images from both modalities were obtained from 15 patients with hepatocellular carcinoma who underwent hepatic radioembolization using Y-90 glass microspheres. Quantitative SPECT and PET images were rigidly registered and the total liver activities and activity distributions estimated for each modality were compared. The activity distributions were compared using profiles, voxel-by-voxel correlation and Bland-Altman analyses, and activity-volume histograms. RESULTS: The mean ± standard deviation of difference in the total activity in the liver between the two modalities was 0% ± 9% (range -21%-18%). Voxel-by-voxel comparisons showed a good agreement in regions corresponding roughly to treated tumor and treated normal liver; the agreement was poorer in regions with low or no expected activity, where PET appeared to overestimate the activity. The correlation coefficients between intrahepatic voxel pairs for the two modalities ranged from 0.86 to 0.94. Cumulative activity volume histograms were in good agreement. CONCLUSIONS: These data indicate that, with appropriate reconstruction methods and measured calibration correction factors, either Y-90 SPECT/CT or Y-90 PET/CT can be used for quantitative post-therapy monitoring of Y-90 activity distribution following hepatic radioembolization.
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Embolización Terapéutica , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada de Emisión de Fotón Único , Radioisótopos de Itrio , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana EdadRESUMEN
Clinical reports of limited and treatable cancer metastases, a disease state that exists in a transitional zone between localized and widespread systemic disease, were noted on occasion historically and are now termed oligometastasis. The ramification of a diagnosis of oligometastasis is a change in treatment paradigm, i.e. if the primary cancer site (if still present) is controlled, or resected, and the metastatic sites are ablated (surgically or with radiation), a prolonged disease-free interval, and perhaps even cure, may be achieved. Contemporary molecular diagnostics are edging closer to being able to determine where an individual metastatic deposit is within the continuum of malignancy. Preclinical models are on the outset of laying the groundwork for understanding the oligometastatic state. Meanwhile, in the clinic, patients are increasingly being designated as having oligometastatic disease and being treated owing to improved diagnostic imaging, novel treatment options with the potential to provide either direct or bridging therapy, and progressively broad definitions of oligometastasis.
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Metástasis de la Neoplasia/fisiopatología , Animales , Teorema de Bayes , Carcinoma/secundario , Carcinoma/terapia , Ensayos Clínicos como Asunto , Criocirugía , Medicina Basada en la Evidencia , Humanos , Escisión del Ganglio Linfático , Irradiación Linfática , Metástasis Linfática , Melanoma/secundario , Melanoma/terapia , Ratones , MicroARNs/genética , Modelos Biológicos , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/terapia , Especificidad de Órganos , ARN Neoplásico/genética , Radiocirugia , Sarcoma/secundario , Sarcoma/terapia , Carga Tumoral , Escape del Tumor , Microambiente TumoralRESUMEN
This case of oligometastatic prostate cancer to the foot highlights the importance of: 1) metastasis remaining high in the differential for unexplained malady, in the setting of a primary cancer, despite an atypical presentation, and 2) comparing sequential imaging studies to baseline images, especially when remote, because subtle findings can declare themselves over time.
RESUMEN
PURPOSE: To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. METHODS: Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4-75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100-300 µm beads loaded with ≤100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. RESULTS: DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p < 0.0003) and a 56 % decrease in tumor enhancement (p < 0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. CONCLUSIONS: Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Sistema Biliar/lesiones , Quimioembolización Terapéutica/efectos adversos , Doxorrubicina/uso terapéutico , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Tumores Neuroendocrinos/patología , Anciano , Medios de Contraste , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Microesferas , Selección de Paciente , Resultado del Tratamiento , Carga TumoralRESUMEN
PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) and sorafenib in patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS A prospective single-center phase II study was undertaken involving patients with unresectable HCC. The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE. Safety and response were assessed. Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients: mean age, 63 years; Child's A, 89%; Barcelona Clinic Liver Cancer stage C, 64%; Eastern Cooperative Oncology Group performance status of 0 and 1, 46% and 54%, respectively; and mean index tumor size, 7.7 cm (standard deviation, ± 4.2 cm). Patients underwent 128 cycles of therapy (sorafenib plus DEB-TACE, 60 cycles; sorafenib alone, 68 cycles). Median number of cycles per patient was two (range, one to five cycles); median number of days treated with sorafenib was 71 (range, 4 to 620 days). The most common toxicities during cycle one were fatigue (94%), anorexia (67%), alterations in liver enzymes (64%), and dermatologic adverse effects (48%). Although most patients experienced at least one grade 3 to 4 toxicity, most toxicities were minor (grade 1 to 2, 83% v grade 3 to 4, 17%). Toxicity during cycle two was decreased. Over the course of the study, there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions. Sorafenib plus DEB-TACE was associated with a disease control rate of 95% (Response Evaluation Criteria in Solid Tumors Group)/100% (European Association for the Study of the Liver [EASL]), with an objective response of 58% (EASL). CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe, with most toxicities related to sorafenib. Toxicity is manageable with dose adjustment of sorafenib. Preliminary efficacy data are promising.