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1.
J Vasc Interv Radiol ; 34(9): 1547-1555, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37210030

RESUMEN

PURPOSE: To evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: This prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. RESULTS: Twenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9-7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0-33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8-31.0 months) versus 10.7 months (95% CI, 8.0-13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7-20.7 months) versus 37.3 months (95% CI, 16.5-58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. CONCLUSIONS: First-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Femenino , Anciano , Estudios Prospectivos , Conductos Biliares Intrahepáticos , Microesferas , Estudios de Factibilidad , Resultado del Tratamiento , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/radioterapia , Radioisótopos de Itrio , Embolización Terapéutica/métodos , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/radioterapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia
2.
Cancer ; 128(3): 461-470, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34643945

RESUMEN

Uncontrolled chemotherapy-induced nausea and vomiting can reduce patients' quality of life and may result in premature discontinuation of chemotherapy. Although nausea and vomiting are commonly grouped together, research has shown that antiemetics are clinically effective against chemotherapy-induced vomiting (CIV) but less so against chemotherapy-induced nausea (CIN). Nausea remains a problem for up to 68% of patients who are prescribed guideline-consistent antiemetics. Despite the high prevalence of CIN, relatively little is known regarding its etiology independent of CIV. This review summarizes a metagenomics approach to the study and treatment of CIN with the goal of encouraging future research. Metagenomics focuses on genetic risk factors and encompasses both human (ie, host) and gut microbial genetic variation. Little work to date has focused on metagenomics as a putative biological mechanism of CIN. Metagenomics has the potential to be a powerful tool in advancing scientific understanding of CIN by identifying new biological pathways and intervention targets. The investigation of metagenomics in the context of well-established demographic, clinical, and patient-reported risk factors may help to identify patients at risk and facilitate the prevention and management of CIN.


Asunto(s)
Antieméticos , Antineoplásicos , Neoplasias , Antieméticos/uso terapéutico , Antineoplásicos/uso terapéutico , Humanos , Metagenómica , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Náusea/prevención & control , Neoplasias/inducido químicamente , Neoplasias/tratamiento farmacológico , Calidad de Vida , Vómitos/inducido químicamente
3.
Curr Oncol Rep ; 24(12): 1821-1828, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36192517

RESUMEN

PURPOSE OF REVIEW: Biliary tract cancers (BTCs) are a heterogenous group of cancers arising from the biliary tract. The hallmark of these cancers is the advanced stage of presentation and a paucity of durable treatment options. Despite the advances in targeted therapy and immunotherapy in solid tumors, systemic cytotoxic chemotherapy has remained the mainstay for cholangiocarcinomas. RECENT FINDINGS: With advances in the understanding of the tumor microenvironment, genetic features, and inflammatory milieu, have led to the identification of tumor-infiltrating immune cells as indicators of prognosis and response to treatment in BTC. Through an improved comprehension of immunology, immuno-oncology is becoming another pillar of treatment along with traditional radiation, surgery, cytotoxic chemotherapy, and targeted therapies. This article reviews the evidence for immunotherapy use in cholangiocarcinoma, which still being in infancy, and offers promising new novel options for the management of biliary tract cancers.


Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Humanos , Neoplasias del Sistema Biliar/terapia , Inmunoterapia , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Factores Inmunológicos/uso terapéutico , Conductos Biliares Intrahepáticos/patología , Microambiente Tumoral
4.
Cancer ; 127(8): 1293-1300, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33289918

RESUMEN

BACKGROUND: Biliary tract cancer (BTC) has a poor prognosis despite treatment with first-line gemcitabine and cisplatin. In BTC, PI3K/AKT pathway activation has been shown to increase resistance to chemotherapy, which may be overcome with PI3K inhibition. This phase 2 study evaluated the safety and efficacy of copanlisib, a PI3K inhibitor, with gemcitabine and cisplatin in advanced BTCs. The role of PTEN expression in outcomes was also explored. METHODS: Patients with advanced/unresectable BTC received gemcitabine, cisplatin, and copanlisib as their first-line treatment. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were the response rate (RR), median overall survival (OS)/PFS, and safety profile. An assessment of PTEN expression by immunohistochemistry was also performed along with molecular profiling. RESULTS: Twenty-four patients received at least 1 dose of the study drug. The PFS rate at 6 months was 51%; the median OS was 13.7 months (95% CI, 6.8-18.0 months), and the median PFS was 6.2 months (95% CI, 2.9-10.1 months). Nineteen patients were evaluable for RR: 6 patients achieved a partial response (31.6%), and 11 (57.9%) had stable disease. The most common grade 3/4 adverse events were a decreased neutrophil count (45.83%), anemia (25%), increased lipase (25%), and hypertension (20.8%). Twenty patients had tissue evaluable for the PTEN status. The PFS for low (n = 9) and high PTEN expression (n = 11) was 8.5 and 4.6 months, respectively (P = .19). The median OS for low and high PTEN expression groups was 17.9 and 7.0 months, respectively (P = .19). CONCLUSIONS: The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered. LAY SUMMARY: The addition of copanlisib, a PI3K inhibitor, to standard chemotherapy for advanced biliary tract cancers was assessed for efficacy and safety. Twenty-four patients with advanced biliary tract cancer received treatment in this study. There was no difference in survival with the addition of copanlisib in comparison with standard chemotherapy. Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Colangiocarcinoma/tratamiento farmacológico , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Pirimidinas/uso terapéutico , Quinazolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/metabolismo , Neoplasias del Sistema Biliar/patología , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Vesícula Biliar/efectos de los fármacos , Vesícula Biliar/metabolismo , Vesícula Biliar/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Medicina de Precisión , Supervivencia sin Progresión , Gemcitabina
5.
Br J Cancer ; 124(11): 1803-1808, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33828254

RESUMEN

BACKGROUND: MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC. METHODS: This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively. CONCLUSION: Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC. CLINICALTRIALS. GOV IDENTIFIER: NCT03332498.


Asunto(s)
Adenina/análogos & derivados , Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Piperidinas/administración & dosificación , Adenina/administración & dosificación , Adenina/efectos adversos , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Reparación de la Incompatibilidad de ADN/genética , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Metástasis de la Neoplasia , Piperidinas/efectos adversos , Supervivencia sin Progresión , Resultado del Tratamiento , Adulto Joven
6.
Ann Surg Oncol ; 28(3): 1845-1858, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32776184

RESUMEN

Precision medicine with genetic profiling of tumor tissue has become an essential part of routine clinical practice in colorectal cancer. However, tissue genetic profiling suffers from clonal evolution, tumor heterogeneity, and time needed to deliver critical information for prompt clinical decision making. In contrast, liquid biopsy with plasma circulating tumor DNA provides genetic and epigenetic information from both the primary and metastatic colorectal cancer, which can potentially capture tumor heterogeneity and evolution with time and treatment. In addition, liquid biopsy with circulating tumor DNA is minimally invasive, quicker, and easily repeatable with high patient compliance to provide both qualitative and quantitative molecular information in real-time. We provide an overview on the potential clinical applications of circulating tumor DNA in the screening, surveillance, and treatment monitoring of colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Detección Precoz del Cáncer , Humanos , Biopsia Líquida , Células Neoplásicas Circulantes
7.
Rep Pract Oncol Radiother ; 26(1): 29-34, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33948299

RESUMEN

BACKGROUND: The purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T). MATERIALS AND METHODS: An exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET. RESULTS: The patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs. TRG 1-3; 91% accuracy in predicting TRG 0-1 vs. TRG 2-3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs. intermediate vs. high NAR scores. CONCLUSION: The pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation.

8.
Cancer ; 126(15): 3464-3470, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32453456

RESUMEN

BACKGROUND: Regorafenib is an oral multikinase inhibitor targeting angiogenesis, oncogenesis, and cancer proliferation/metastasis. This study evaluated the efficacy of regorafenib in refractory biliary tract cancer (BTC) in a multi-institutional phase 2 study. METHODS: Patients with BTC who progressed on at least 1 line of systemic therapy received regorafenib at 160 mg daily for 21 days on and 7 days off. The primary endpoint was 6-month overall survival (OS), and the secondary endpoints were median OS, progression-free survival (PFS), and objective response rates. Pretreatment plasma was collected for cytokine evaluation. RESULTS: A total of 39 patients were enrolled, and 33 were evaluable for efficacy. The median PFS and OS were 3.7 and 5.4 months, respectively, with survival rates of 46.2% at 6 months, 35.9% at 12 months, and 25.6% at 18 months for the intention-to-treat population. For the 33 evaluable patients who received regorafenib for at least 3 weeks, the median PFS and OS were 3.9 and 6.7 months, respectively, with survival rates of 51.5% at 6 months, 39.4% at 12 months, and 27.3% at 18 months. The objective response rate was 9.1%, and the disease control rate was 63.6%. Twenty-eight patients (71.8%) experienced grade 3/4 adverse events. Among the 23 cytokines analyzed, elevated baseline vascular endothelial growth factor D (VEGF-D) was associated with shorter PFS, whereas elevated baseline interleukin 6 (IL-6) and glycoprotein 130 (GP130) were associated with shorter OS. CONCLUSIONS: Regorafenib demonstrated modest clinical efficacy in heavily pretreated patients with BTC. Further exploration of biomarkers is warranted to identify a group of patients with BTC who may benefit from regorafenib.


Asunto(s)
Neoplasias del Sistema Biliar/tratamiento farmacológico , Colangiocarcinoma/tratamiento farmacológico , Compuestos de Fenilurea/administración & dosificación , Piridinas/administración & dosificación , Factor D de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Neoplasias del Sistema Biliar/epidemiología , Neoplasias del Sistema Biliar/genética , Neoplasias del Sistema Biliar/patología , Colangiocarcinoma/epidemiología , Colangiocarcinoma/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/efectos adversos , Supervivencia sin Progresión , Piridinas/efectos adversos
9.
J Vasc Interv Radiol ; 31(4): 584-591, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31471193

RESUMEN

PURPOSE: To evaluate the safety and efficacy of partial splenic embolization (PSE) in cancer patients with different etiologies of splenomegaly/hypersplenism. MATERIALS AND METHODS: The medical records of 35 cancer patients who underwent 39 PSE procedures were analyzed. The splenomegaly/hypersplenism was due to chemotherapy (n = 17), portal hypertension (n = 10), or hematologic malignancy (n = 8). After the first 11 PSEs, celiac plexus neurolysis, corticosteroids, and non-steroid anti-inflammatory drugs (NSAIDs) were included in the post-procedural management. RESULTS: PSE led to 59 ± 16% (mean ± standard deviation) splenic infarcts. The infarct volume per 1 mL 300-500 µm tris-acryl gelatin microspheres was not significantly different between the chemotherapy-induced group (264 ± 89 cm3) and the portal hypertension group (285 ± 139 cm3) but was significantly higher in the hematology group (582 ± 345 cm3). Platelet count increased from 65.7 ± 19.7 k/µl to a peak platelet count of 221 ± 83 k/µl at 2 weeks after PSE. Patients with a follow-up period of more than 1 year had the most recent platelet count of 174 ± 113 k/µl. Platelet count increase was significantly higher in the chemotherapy-induced group than the portal hypertension group. Adding celiac plexus neurolysis, corticosteroids, and NSAIDs to the post-procedural management resulted in a decreased rate of major complications from 73% to 46% and a decrease in the rate of moderate or severe pain from 92% to 20%. CONCLUSIONS: PSE improved platelet counts in cancer patients despite different etiologies of splenomegaly. The addition of celiac plexus neurolysis, corticosteroids, and NSAIDS to the post-PSE treatment protocol reduced complications. Data from this study could help to predict the amount of 300-500 µm tris-acryl gelatin microspheres required to achieve a planned infarct size.


Asunto(s)
Antineoplásicos/efectos adversos , Embolización Terapéutica , Hipertensión Portal/etiología , Neoplasias/tratamiento farmacológico , Presión Portal , Arteria Esplénica , Esplenomegalia/terapia , Anciano , Plaquetas , Embolización Terapéutica/efectos adversos , Femenino , Neoplasias Hematológicas/complicaciones , Humanos , Hipertensión Portal/diagnóstico , Hipertensión Portal/fisiopatología , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Estudios Retrospectivos , Arteria Esplénica/diagnóstico por imagen , Esplenomegalia/sangre , Esplenomegalia/diagnóstico por imagen , Esplenomegalia/etiología , Factores de Tiempo , Resultado del Tratamiento
10.
Future Oncol ; 16(30): 2411-2420, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32686956

RESUMEN

Aim: Genomic-based risk stratification to personalize radiation dose in rectal cancer. Patients & methods: We modeled genomic-based radiation dose response using the previously validated radiosensitivity index (RSI) and the clinically actionable genomic-adjusted radiation dose. Results: RSI of rectal cancer ranged from 0.19 to 0.81 in a bimodal distribution. A pathologic complete response rate of 21% was achieved in tumors with an RSI <0.31 at a minimal genomic-adjusted radiation dose of 29.76 when modeling RxRSI to the commonly prescribed physical dose of 50 Gy. RxRSI-based dose escalation to 55 Gy in tumors with an RSI of 0.31-0.34 could increase pathologic complete response by 10%. Conclusion: This study provides a theoretical platform for development of an RxRSI-based prospective trial in rectal cancer.


Asunto(s)
Genómica , Medicina de Precisión , Dosificación Radioterapéutica , Neoplasias del Recto/genética , Neoplasias del Recto/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada/métodos , Relación Dosis-Respuesta en la Radiación , Femenino , Perfilación de la Expresión Génica , Genómica/métodos , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Oportunidad Relativa , Medicina de Precisión/métodos , Tolerancia a Radiación/genética , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/mortalidad , Transcriptoma , Resultado del Tratamiento
11.
Cancer ; 124(15): 3118-3126, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29905927

RESUMEN

BACKGROUND: Regorafenib, a multikinase inhibitor that inhibits angiogenesis, growth, and proliferation, prolongs survival as monotherapy in patients with refractory colorectal cancer. This international, double-blind, placebo-controlled, multicenter trial assessed the efficacy of regorafenib with folinic acid, fluorouracil, and irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer who progressed on first-line oxaliplatin and fluoropyrimidine enrolled at 45 sites in the United States and Ireland. Patients, stratified by prior bevacizumab use, were randomized 2:1 to regorafenib or placebo. The treatment consisted of FOLFIRI on days 1 and 2 and days 15 and 16 with 160 mg of regorafenib or placebo on days 4 to 10 and days 18 to 24 of every 28-day cycle. Crossover was not allowed. The primary endpoint was progression-free survival (PFS). Under the assumption of a 75% event rate, 180 patients were required for 135 events to achieve 90% power to detect a hazard ratio (HR) of 0.65 with a 1-sided α value of .1. RESULTS: One hundred eighty-one patients were randomized (120 to regorafenib-FOLFIRI and 61 to placebo-FOLFIRI) with a median age of 62 years. Among these, 117 (65%) received prior bevacizumab or aflibercept. PFS was longer with regorafenib-FOLFIRI than placebo-FOLFIRI (median, 6.1 vs 5.3 months; HR, 0.73; 95% confidence interval [CI], 0.53-1.01; log-rank P = .056). The median overall survival was not longer (HR, 1.01; 95% CI, 0.71-1.44). The response rate was higher with regorafenib-FOLFIRI (34%; 95% CI, 25%-44%) than placebo-FOLFIRI (21%; 95% CI, 11%-33%; P = .07). Grade 3/4 adverse events with a >5% absolute increase from regorafenib included diarrhea, neutropenia, febrile neutropenia, hypophosphatemia, and hypertension. CONCLUSIONS: The addition of regorafenib to FOLFIRI as second-line therapy for metastatic colorectal cancer only modestly prolonged PFS over FOLFIRI alone. Cancer 2018. © 2018 American Cancer Society.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos de Fenilurea/administración & dosificación , Piridinas/administración & dosificación , Adulto , Anciano , Camptotecina/administración & dosificación , Neoplasias Colorrectales/patología , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán/administración & dosificación , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión
12.
J Vasc Interv Radiol ; 29(8): 1101-1108, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30042074

RESUMEN

PURPOSE: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. RESULTS: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. CONCLUSIONS: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.


Asunto(s)
Neoplasias de los Conductos Biliares/radioterapia , Colangiocarcinoma/radioterapia , Embolización Terapéutica/métodos , Radiofármacos/administración & dosificación , Radioisótopos de Itrio/administración & dosificación , Anciano , Anciano de 80 o más Años , Aspartato Aminotransferasas/sangre , Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Bilirrubina/sangre , Antígeno CA-19-9/sangre , Colangiocarcinoma/sangre , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/mortalidad , Femenino , Vidrio , Humanos , Relación Normalizada Internacional , Estimación de Kaplan-Meier , Masculino , Microesferas , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Radiofármacos/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica Humana/metabolismo , Factores de Tiempo , Resultado del Tratamiento , Radioisótopos de Itrio/efectos adversos
13.
Oncology ; 92(4): 190-196, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28152526

RESUMEN

BACKGROUND: Although squamous cell anal carcinomas are relatively rare, their incidence has been increasing steadily. Because of the limited data, treatment of metastatic disease is a major therapeutic challenge. In this study, we report the safety and efficacy of epidermal growth factor receptor (EGFR) inhibitors in patients with advanced squamous cell anal carcinomas. METHOD: A retrospective analysis was conducted using the Moffitt Cancer Tumor Registry from January 2009 to January 2014. Eligible patients had diagnosis of advanced squamous cell anal carcinomas and received an EGFR inhibitor as part of their treatment. RESULT: A total of 13 patients were identified for analysis. All of them received concurrent chemoradiation as initial treatment and subsequently had recurrence. Five patients received single agent cetuximab or panitumumab, and the others received cetuximab or panitumumab with irinotecan or FOLFIRI. The objective response rate was 30.8% including 1 complete response, and the disease control rate was 46.2%. With a median follow-up of 9.6 months, the median progression-free survival and median overall survival were 4.4 months and 11.4 months, respectively. CONCLUSION: Our analysis suggests that EGFR inhibitors have potential efficacy and are reasonably well tolerated in patients with squamous cell anal carcinomas. These findings warrant further evaluation in a large prospective trial.


Asunto(s)
Neoplasias del Ano/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Ano/radioterapia , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Carcinoma de Células Escamosas/radioterapia , Cetuximab/administración & dosificación , Cetuximab/efectos adversos , Cetuximab/uso terapéutico , Quimioradioterapia/efectos adversos , Femenino , Florida , Fluorouracilo/uso terapéutico , Humanos , Irinotecán , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Panitumumab , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento
14.
Cancer ; 122(18): 2828-35, 2016 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-27244218

RESUMEN

BACKGROUND: The incidence and outcomes of patients with colorectal cancer (CRC) varies by age. Younger patients tend to have sporadic cancers that are not detected by screening and worse survival. To understand whether genetic differences exist between age cohorts, the authors sought to characterize unique genetic alterations in patients with CRC. METHODS: In total, 283 patients who were diagnosed with sporadic CRC between 1998 and 2010 were identified and divided by age into 2 cohorts-ages ≤45 years (the younger cohort) and ≥65 years (the older cohort)-and targeted exome sequencing was performed. The Fisher exact test was used to detect differences in mutation frequencies between the 2 groups. Whole exome sequencing was performed on 21 additional younger patient samples for validation. Findings were confirmed in The Cancer Genome Atlas CRC data set. RESULTS: In total, 246 samples were included for final analysis (195 from the older cohort and 51 from the younger cohort). Mutations in the FBXW7 gene were more common in the younger cohort (27.5% vs 9.7%; P = .0022) as were mutations in the proofreading domain of polymerase ε catalytic subunit (POLE) (9.8% vs 1%; P = .0048). There were similar mutation rates between cohorts with regard to TP53 (64.7% vs 61.5%), KRAS (43.1% vs 46.2%), and APC (60.8% vs 73.8%). BRAF mutations were numerically more common in the older cohort, although the difference did not reach statistical significance (2% vs 9.7%; P = .082). CONCLUSIONS: In this retrospective study, a unique genetic profile was identified for younger patients who have CRC compared with patients who are diagnosed at an older age. These findings should be validated in a larger study and could have an impact on future screening and treatment modalities for younger patients with CRC. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2828-2835. © 2016 American Cancer Society.


Asunto(s)
Proteínas de Ciclo Celular/genética , Neoplasias Colorrectales/genética , ADN Polimerasa II/genética , Proteínas F-Box/genética , Ubiquitina-Proteína Ligasas/genética , Factores de Edad , Anciano , Anciano de 80 o más Años , Proteínas de Ciclo Celular/metabolismo , Estudios de Cohortes , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , ADN Polimerasa II/metabolismo , Proteínas F-Box/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Unión a Poli-ADP-Ribosa , Estudios Retrospectivos , Ubiquitina-Proteína Ligasas/metabolismo
15.
J Surg Oncol ; 114(2): 170-5, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27158031

RESUMEN

INTRODUCTION: Ampullary adenocarcinoma (AAC) is a rare neoplasm. We sought to determine the clinicopathologic factors contributing to the overall survival (OS) and recurrence-free (RFS) survival. METHODS: Patients (pts) with resected AAC were identified from 1996 to 2015 and reviewed for clinicopathologic factors and correlated with outcome. RESULTS: We identified and evaluated 106 pts diagnosed with AAC. The median age was 70.2 years (range 41-86) and 60 (56.6%) were male. Overall, 105 pts (99.1%) had a pancreaticoduodenectomy. An R0 resection was achieved in 101 (95%) pts. Median follow-up was 19 months with a median OS of 49.3 months. Lymph node metastasis and poorly differentiated tumors adversely affected OS on multivariate analysis (MVA). Twenty patients (18.9%) developed recurrence. The median RFS was 27 months. RFS was adversely affected by lymph node count and metastasis, tumor differentiation, and histological subtype on MVA. Survival was not affected by the addition of adjuvant therapy. Retrieval of ≤12 lymph nodes and lymph node ratio ≥0.10 resulted in worse OS on Kaplan-Meier analysis. CONCLUSIONS: Our data show retrieval of ≤12 nodes, involvement of nodes with AAC, moderately or poorly differentiated tumors, and pancreaticobiliary subtype adversely affected survival, while the use of adjuvant therapy demonstrated no significant benefit. J. Surg. Oncol. 2016;114:170-175. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Adenocarcinoma , Neoplasias del Conducto Colédoco , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pancreaticoduodenectomía , Resultado del Tratamiento
17.
Expert Opin Investig Drugs ; 33(2): 145-157, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38275174

RESUMEN

INTRODUCTION: Anal cancer, a rare malignancy accounting for 2.5-3.0% of gastrointestinal cancers, primarily manifests as squamous cell carcinoma associated with HPV. Recent years have witnessed significant advancements in managing squamous cell carcinoma of the anus (SCCA), particularly with the introduction of immune checkpoint inhibitors (ICIs) and randomized data on front-line chemotherapy. AREAS COVERED: This review discusses the current standard treatments for both early and advanced SCCA, based on published data. The authors then describe the new approaches, focusing on ICI combinations, targeted agents, T-cell adoptive therapy, and HPV-therapeutic vaccines. EXPERT OPINION: The current standard treatment for SCCA includes front-line carboplatin and paclitaxel, with pembrolizumab and nivolumab as later-line options. While modified DCF has shown promise in single-arm studies, its role as a front-line therapy requires confirmation through randomized data. We eagerly anticipate the results of phase 3 trials investigating the front-line chemo-immunotherapy for metastatic SCCA and ICI consolidation following chemoradiation for early-stage SCCA. Novel approaches like T-cell adoptive therapy, HPV-therapeutic vaccines, and bifunctional antibodies combined with HPV vaccines are in early-stage trials for HPV-mediated tumors, including HPV-positive SCCA. These approaches targeting HPV epitopes may eventually gain tumor-agnostic approval, although their role in SCCA may take time to establish.


Asunto(s)
Neoplasias del Ano , Drogas en Investigación , Humanos , Neoplasias del Ano/tratamiento farmacológico , Neoplasias del Ano/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Drogas en Investigación/farmacología , Drogas en Investigación/uso terapéutico , Infecciones por Papillomavirus/complicaciones , Vacunas , Ensayos Clínicos Controlados Aleatorios como Asunto
18.
Pragmat Obs Res ; 15: 79-87, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881691

RESUMEN

Lenvatinib received its initial approval in 2018 for the treatment of advanced hepatocellular carcinoma. It has since emerged as the preferred first line agent, supported by non-inferiority data from the REFLECT trial. Notably, lenvatinib exhibits a more favorable toxicity profile and a higher response rate compared to sorafenib. Despite the approval of immunotherapy in 2020, specifically the combination of atezolizumab and bevacizumab following the IMbrave150 trial, tyrosine kinase inhibitors remain an indispensable class of agents in the landscape of hepatocellular carcinoma treatment. This comprehensive review delves into various facets of lenvatinib utilization in hepatocellular carcinoma, shedding light on real-world data, addressing challenges, and providing insights into strategies to overcome these obstacles.

19.
J Gastrointest Oncol ; 15(1): 485-490, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38482231

RESUMEN

Background: Cholangiocarcinoma (CCA) is a rare and aggressive gastrointestinal cancer. Unfortunately, 60% to 70% of early-stage CCA patients experience disease recurrence after curative resection and standard adjuvant therapy. Currently, there is no reliable tool to identify CCA recurrence before radiographic detection. Longitudinal monitoring of circulating tumor DNA (ctDNA) has shown promising value in molecular identification of relapse prior to conventional surveillance in other solid tumors. However, there is a scarcity of data on ctDNA in CCA after curative surgery. Case Description: An 81-year-old male with stage 3A intrahepatic CCA achieved radiographic remission after curative resection and was started on standard adjuvant capecitabine on post-operative day (POD) 50. Tumor-informed ctDNA tested positive on two consecutive occasions, with the titer increasing from 0.16 mean tumor molecule (MTM)/mL on POD 92 to 0.80 MTM/mL on POD 183, despite being on capecitabine. carbohydrate antigen 19-9 (CA19-9) also continued to increase from 175.6 U/mL on POD 92 to 7,594.9 U/mL on POD 217. Notably, surveillance computed tomography (CT) scans showed no evidence of disease (NED) on POD 126, 186, and 211. Molecular profiling and next-generation sequencing (NGS) panels from CCA tissue revealed microsatellite instability-high (MSI-H). After extensive discussions with the patient regarding the rising ctDNA titer despite being on capecitabine for nearly 6 months, we initiated pembrolizumab on POD 224 prior to radiographic recurrence. Given the tumor is MSI-H, and the preferred toxicity profile compared to the front-line chemotherapy option for CCA, we started pembrolizumab. ctDNA became undetectable, and CA19-9 returned to the reference range with pembrolizumab. As of the last follow-up on POD 876, the patient has continued pembrolizumab without noticeable side effects, and imaging continues to show NED, with persistent negative ctDNA and normal CA19-9 levels. Conclusions: This case demonstrates the potential utility of tumor-informed ctDNA in CCA as (I) an early detection tool before radiographic recurrence; (II) a response monitoring tool as a surrogate biomarker that can guide therapy optimization; and (III) shows that early intervention with immunotherapy or potentially targeted agents based on ctDNA may lead to improved survival outcomes.

20.
Cancers (Basel) ; 16(3)2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38339307

RESUMEN

Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples from the patients in the trial were collected and evaluated to discover potential biomarkers. The obtained samples were assessed for immunohistochemistry, ELISA and RNA sequencing. Their correlations with clinical outcome were analyzed. A high albumin level was significantly associated with improved progression-free survival (PFS), overall survival (OS) and disease control. Non-liver metastatic disease showed prolonged PFS and OS. Low regulatory T-cell (Treg) infiltration correlated with prolonged PFS. Low MIP-1ß was associated with durable response and improved OS significantly. Upregulation of 23 genes, including CAPN9, NAPSA and ROS1, was observed in the durable disease control group, and upregulation of 10 genes, including MRPS18A, MAIP1 and CMTR2, was associated with a statistically significant improvement of PFS. This study suggests that pretreatment albumin, MIP-1ß, non-liver metastatic disease and Treg infiltration may be potential predictive biomarkers of regorafenib/nivolumab in pMMR colorectal cancer. Further studies are needed to confirm these findings.

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