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1.
Oncologist ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39293067

RESUMEN

BACKGROUND: Doublet platinum or taxane-based therapies are the current standard backbone of treatment for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Previously used anthracycline-based triplet regimens are no longer used routinely due to toxicity and lack of superior efficacy. We hypothesized that the addition of nab-paclitaxel to FOLFOX (FOLFOX-A) would induce higher efficacy and better tolerability. PATIENTS AND METHODS: Eligible patients with chemotherapy-naïve advanced unresectable HER2-negative gastric or GEJ adenocarcinoma were enrolled in this phase II single-arm trial of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2 over 46-48 hours) + nab-paclitaxel (150 mg/m2) every 14 days of a 28-day cycle. Evaluable disease according to RECIST v1.1 for solid tumors was required. The primary endpoint was the objective response rate. Simon's optimal 2-stage design was used to test 5% versus 20% response rate with 90% power and 10% one-sided type I error rate. RESULTS: The study enrolled 39 patients. Median age was 63 (range 20-80) years, 30 (77%) were male, 34 (94%) were White, and 21 (57%) had gastric tumors. The median number of cycles completed was 4.5 (range: 0-36), and 25 patients required dose reductions or discontinuation of at least one component due to toxicity. Of the 38 patients evaluable for response, 15 (42.9%) had complete/partial response (CR/PR) as the best response, and 13 (37.1%) had stable disease. progression-free survival (PFS) and OS data were available for 38 patients, with a median follow-up duration of 27 months (range: 18.2-51.9 months for censored patients). Median PFS was 6.6 months (95% CI: 5.6-12.9), with 31.0% (95% CI: 18.4%-52.4%) 12-month PFS rate. The median OS was 10.5 months (95% CI: 8.8-20.7), 12-month OS rate was 44.7% (95% CI: 31.4%-63.7%). Treatment-related grade 3-4 toxicities included peripheral sensory neuropathy and anemia (18.4% each), neutropenia (15.8%), and diarrhea and lymphopenia (7.9% each). CONCLUSIONS: FOLFOX-A has a significant response rate, expected toxicities, and should be considered for future investigation in combination with immunotherapy given the recent approvals.

2.
J Natl Compr Canc Netw ; 22(6): 366-375, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-39151454

RESUMEN

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy.


Asunto(s)
Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/patología , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/normas , Terapia Combinada/métodos , Estadificación de Neoplasias , Oncología Médica/normas , Oncología Médica/métodos
3.
J Natl Compr Canc Netw ; 22(2 D)2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38862008

RESUMEN

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.


Asunto(s)
Neoplasias del Colon , Humanos , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/terapia , Neoplasias del Colon/patología , Neoplasias del Colon/tratamiento farmacológico , Oncología Médica/normas , Oncología Médica/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estados Unidos
4.
HPB (Oxford) ; 26(5): 656-663, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38383208

RESUMEN

BACKGROUND: Hepatic artery infusion (HAI) is less frequently used in the adjuvant setting for resectable colorectal liver metastasis (CRLM) due to concerns regarding toxicity. Our objective was to evaluate the safety and feasibility of establishing an adjuvant HAI program. METHODS: Patients who underwent HAI pump placement between January 2019 and February 2023 for CRLM were identified. Complications and HAI delivery were compared between patients who received HAI in the unresectable and adjuvant settings. RESULTS: Of 51 patients, 23 received HAI for unresectable CRLM and 28 in the adjuvant setting. Patients with unresectable CRLM more commonly had bilobar disease (n = 23/23 vs n = 18/28, p < 0.01) and more preoperative liver metastases (median 10 [IQR 6-15] vs 4 [IQR 3-7], p < 0.01). Biliary sclerosis was the most common complication (n = 2/23 vs n = 4/28); however, there were no differences in postoperative or HAI-specific complications. In the most recent two years, 0 patients in the unresectable group vs 2 patients in the adjuvant group developed biliary sclerosis. All patients were initiated on HAI with no difference in treatment times or dose reductions. CONCLUSION: Adjuvant HAI is safe and feasible for patients with resectable CRLM. HAI programs can carefully consider including patients with resectable CRLM if managed by an experienced multidisciplinary team with quality assurance controls in place.


Asunto(s)
Neoplasias Colorrectales , Estudios de Factibilidad , Arteria Hepática , Infusiones Intraarteriales , Neoplasias Hepáticas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Quimioterapia Adyuvante , Resultado del Tratamiento
5.
J Surg Oncol ; 129(1): 78-84, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38063061

RESUMEN

Rectal cancer is a prevalent disease worldwide. The standard treatment of locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy followed by surgery and adjuvant systemic chemotherapy. Studies have been done to determine the best sequence of treatments to improve survival, cure rate and long term toxicity profile. In this paper, we will review the literature regarding the evolution of LARC treatment.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recto/cirugía , Neoplasias del Recto/patología , Quimioradioterapia , Estadificación de Neoplasias
6.
JCO Oncol Pract ; 19(10): e957-e966, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37527464

RESUMEN

PURPOSE: Cancer staging is the foundation for all cancer management decisions. For real-time use, stage must be embedded in the electronic health record as a discrete data element. The objectives of this quality improvement (QI) initiative were to (1) identify barriers to utilization of an existing discrete cancer staging module, (2) identify health information technology (HIT) solutions to support discrete capture of cancer staging data, and (3) increase capture across the oncology enterprise in our diverse health system. METHODS: Six sigma QI methodologies were used to define barriers and solutions to improve discrete cancer staging. Design thinking principles informed solution development to test prototypes. Two multidisciplinary teams of disease-specific clinicians within GI and genitourinary conducted phased testing pilots to determine health system solutions. Solutions were expanded to all oncology specialties across our health system. RESULTS: Baseline average discrete staging capture across our health system was 31%. Poor workflow efficiency, limited accountability, and technical design gaps were key barriers to timely, complete staging. Implementation of more than 25 design enhancements to a HIT solution and passive user alerts led to a postimplementation capture rate of 58% across 55 outpatient clinics involving more than 400 clinicians. CONCLUSION: We identified key barriers to discrete data capture and designed solutions through iterative use of QI methodologies and disease-specific pilots. After implementation, discrete capture of cancer staging nearly doubled across our diverse health system. This approach is scalable and transferable to other initiatives to develop and implement clinically relevant HIT solutions across a diverse health system.

7.
Br J Cancer ; 129(5): 782-790, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37443348

RESUMEN

BACKGROUND: We previously reported activity of pelareorep, pembrolizumab and chemotherapy. Patients developed new T-cell clones and increased peripheral T-cell clonality, leading to an inflamed tumour. To evaluate a chemotherapy-free regimen, this study assesses if pelareorep and pembrolizumab has efficacy by inducing anti-tumour immunological changes (NCT03723915). METHODS: PDAC patients who progressed after first-line therapy, received iv pelareorep induction with pembrolizumab every 21-days. Primary objective is overall response rate. Secondary objectives included evaluation of immunological changes within tumour and blood. RESULTS: Clinical benefit rate (CBR) was 42% amongst 12 patients. One patient achieved partial response (PR) and four stable disease (SD). Seven progressed, deemed non-responders (NR). VDAC1 expression in peripheral CD8+ T cells was higher at baseline in CBR than NR but decreased in CBR upon treatment. On-treatment peripheral CD4+ Treg levels decreased in CBR but not in NR. Analysis of tumour demonstrated PD-L1+ cells touching CD8+ T cells, and NK cells were more abundant post-treatment vs. baseline. A higher intensity of PD-L1 in tumour infiltrates at baseline, particularly in CBR vs. NR. Finally, higher levels of soluble (s)IDO, sLag3, sPD-1 observed at baseline among NR vs. CBR. CONCLUSION: Pelareorep and pembrolizumab showed modest efficacy in unselected patients, although potential immune and metabolic biomarkers were identified to warrant further evaluation.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos/metabolismo
8.
J Natl Compr Canc Netw ; 21(6): 653-677, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37308125

RESUMEN

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.


Asunto(s)
Neoplasias del Ano , Carcinoma de Células Escamosas , Humanos , Biopsia , Oncología Médica
9.
CNS Oncol ; 12(3): CNS99, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37219390

RESUMEN

Materials & methods: We recently reported the largest trial of breast cancer patients with HER2 positive leptomeningeal metastases (LM) treated with trastuzumab. An additional treatment indication was explored as part of a single institution retrospective case series of HER2 positive esophageal adenocarcinoma LM (n = 2). Results: One patient received intrathecal trastuzumab (80 mg twice weekly) as part of their treatment regimen with durable long-term response and clearance of circulating tumor cells in the cerebral spinal fluid. The other patient demonstrated rapid progression and death as previously described in the literature. Conclusion: Intrathecal trastuzumab is a well-tolerated and reasonable therapeutic option worthy of further exploration for patients with HER2 positive esophageal carcinoma LM. An associative, but not a causal relationship, can be made regarding therapeutic intervention.


Cancer of the esophagus, the tube that connects the mouth to the stomach, tends to be aggressive. Very rarely, this cancer can spread to the lining that surrounds your brain, called the leptomeninges. Previous reports of patients who have experienced this specific spreading pattern of esophageal cancer to the leptomeninges are quite grim, with patients experiencing rapid decline and death within weeks to months. However, we write with two cases of esophageal cancer with this leptomeningeal spreading pattern, one of which involves a patient treated with a medication known as trastuzumab. As part of his long and complex course of treatment, this patient was given trastuzumab through a tube traveling directly to the area of the leptomeninges. This patient, now almost 2 years out from his initial diagnosis, has responded well to the treatment. As such, we believe that this specific treatment regimen as well as the ways in which our clinical team tracked this patient's response to medications are worth exploring further.


Asunto(s)
Neoplasias de la Mama , Carcinoma , Carcinomatosis Meníngea , Humanos , Femenino , Estudios Retrospectivos , Receptor ErbB-2/uso terapéutico , Trastuzumab/efectos adversos , Neoplasias de la Mama/patología , Carcinomatosis Meníngea/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
10.
Oncologist ; 28(9): 827-e822, 2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37104870

RESUMEN

BACKGROUND: Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers. METHODS: The primary endpoint was progression-free survival (PFS); 87 patients (43 in arm A, 44 in arm B) were treated. RESULTS: Median PFS was 2.6 months in arm A [90% CL 1.8-3.5] and 2.3 months in arm B [90% 2.0-3.5], P = .86. Stable disease was observed in 29 (33%) patients. Objective response rates for Arms A and B were 12% [90% CI, 5-23%] and 14% [90% CI, 6-25%]. Median overall survival was 6.7 months [90% CL 4.9-9.5] in arm A and 7.2 months [90% CL 4.9-8.1] in arm B, P = 56. CONCLUSION: The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes relative to standard of care (ClinicalTrials.gov Identifier: NCT01142388).


Asunto(s)
Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Paclitaxel/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Gástricas/tratamiento farmacológico , Unión Esofagogástrica/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
11.
J Natl Compr Canc Netw ; 21(4): 393-422, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37015332

RESUMEN

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.


Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Neoplasias Primarias Secundarias , Humanos , Calidad de Vida , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/terapia , Unión Esofagogástrica/patología , Carcinoma de Células Escamosas/patología , Neoplasias Primarias Secundarias/patología
12.
Abdom Radiol (NY) ; 48(5): 1709-1723, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36607401

RESUMEN

Gastrointestinal malignancies, though uncommon in pregnancy, present several unique challenges with regards to diagnosis, staging, and treatment. Imaging the pregnant patient with a suspected or confirmed GI malignancy requires modifications to the radiologic modality of choice and protocol in order to minimize harm to the fetus, ensure accuracy in diagnosis and staging and guide treatment decisions. In this review article, we discuss the imaging approach to the pregnant patient with GI cancer, including safe radiologic modalities and modifications to imaging protocols. We also review the most common GI cancers encountered in pregnancy, including colorectal, pancreatic, gastric, and small bowel tumors, with emphasis to imaging findings, staging, and treatment considerations.


Asunto(s)
Neoplasias Gastrointestinales , Complicaciones Neoplásicas del Embarazo , Femenino , Humanos , Embarazo , Neoplasias Gastrointestinales/diagnóstico por imagen , Neoplasias Gastrointestinales/patología
13.
J Natl Compr Canc Netw ; 20(10): 1139-1167, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36240850

RESUMEN

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.


Asunto(s)
Neoplasias del Recto , Humanos , Oncología Médica , Terapia Neoadyuvante , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/patología , Neoplasias del Recto/terapia
14.
Cardiovasc Intervent Radiol ; 45(8): 1117-1128, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35732931

RESUMEN

PURPOSE: Unresectable intrahepatic cholangiocarcinoma (ICC) signifies a poor prognosis with limited treatment options beyond systemic chemotherapy. This study's purpose was to evaluate the safety, efficacy, and potential for downstaging to resection of yttrium-90 (Y90) radioembolization for treatment of unresectable ICC. MATERIALS AND METHODS: From 2004 to 2020, 136 patients with unresectable ICC were treated with radioembolization at a single institution. Retrospective review was performed of a prospectively collected database. Outcomes were (1) biochemical and clinical toxicities, (2) local tumor response, (3) time to progression, and (4) overall survival (OS) after Y90. Univariate/multivariate survival analyses were performed. A subgroup analysis was performed to calculate post-resection recurrence and OS in patients downstaged to resection after Y90. RESULTS: Grade 3+ clinical and biochemical toxicities were 7.6% (n = 10) and 4.9% (n = 6), respectively. Best index lesion response was complete response in 2 (1.5%), partial response in 42 (32.1%), stable disease in 82 (62.6%), and progressive disease in 5 (3.8%) patients. Median OS was 14.2 months. Solitary tumor (P < 0.001), absence of vascular involvement (P = 0.009), and higher serum albumin (P < 0.001) were independently associated with improved OS. Eleven patients (8.1%) were downstaged to resection and 2 patients (1.5%) were bridged to transplant. R0-resection was achieved in 8/11 (72.7%). Post-resection median recurrence and OS were 26.3 months and 39.9 months, respectively. CONCLUSION: Y90 has an acceptable safety profile and high local disease control rates for the treatment of unresectable ICC. Downstaging to resection with > 3 years survival supports the therapeutic role of Y90 for unresectable ICC. LEVEL OF EVIDENCE: Level 3, single-arm single-center cohort study.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Embolización Terapéutica , Neoplasias Hepáticas , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/cirugía , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Radioisótopos de Itrio/uso terapéutico
15.
JCO Precis Oncol ; 6: e2100289, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35772051

RESUMEN

PURPOSE: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for baseline characterization and longitudinal monitoring of a tumor throughout disease management. The aim of this study was to evaluate the utility of ctDNA across a wide spectrum of tumor types. METHODS: We retrospectively identified 1,763 patients with advanced cancers who had next-generation sequencing of ctDNA or tumor tissue completed by a designated commercial assay at Northwestern University. RESULTS: ctDNA identified at least one gene alteration in 90% of patients. The number of detected alterations (NDA) and mutant allele frequency (MAF) of the most frequently mutated genes varied significantly across tumor types, with the highest MAF observed in gastric, colorectal, and breast cancers and the highest NDA observed in colorectal, lung squamous, and ovarian/endometrial cancers. TP53 was the most mutated gene in all tumor types. PIK3CA, ERBB2, BRCA1, and FGFR1 alterations were associated with breast cancer, and ESR1 mutations were exclusively detected in this tumor type. Colorectal cancer was characterized by alterations in KRAS and APC mutations, whereas KRAS, EGFR, PIK3CA, and BRAF mutations were common in lung adenocarcinoma. Concordance between blood and tissue sequencing was notably observed for truncal gene alterations (eg, APC and KRAS), whereas low concordance was often observed in genes associated with treatment resistance mechanisms (eg, RB1 and NF1). Tumor mutational burden (TMB) varied significantly across tumor types, and patients with high MAF or NDA had a significantly higher TMB score with one of the investigated platforms. CONCLUSION: The study provided new insights into the ctDNA mutational landscape across solid tumors, suggesting new hypotheses-generating data and caveats for future histotype-agnostic workflows integrated with tissue-based biomarkers such as TMB.


Asunto(s)
Neoplasias de la Mama , ADN Tumoral Circulante , Neoplasias Colorrectales , Neoplasias Ováricas , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , ADN Tumoral Circulante/genética , Fosfatidilinositol 3-Quinasa Clase I , Femenino , Genómica , Humanos , Proteínas Proto-Oncogénicas p21(ras) , Estudios Retrospectivos
16.
Cancers (Basel) ; 14(9)2022 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-35565336

RESUMEN

Patients with a history of malignancy have been shown to be at an increased risk of COVID-19-related morbidity and mortality. Poorer clinical outcomes in that patient population are likely due to the underlying systemic illness, comorbidities, and the cytotoxic and immunosuppressive anti-tumor treatments they are subjected to. We identified 416 cancer patients with SARS-CoV-2 infection being managed for their malignancy at Northwestern Medicine in Chicago, Illinois, between March and July of 2020. Seventy-five (18.0%) patients died due to COVID-related complications. Older age (>60), male gender, and current treatment with immunotherapy were associated with shorter overall survival. Laboratory findings showed that higher platelet counts, ALC, and hemoglobin were protective against critical illness and death from COVID-19. Conversely, elevated inflammatory markers such as ferritin, d-dimer, procalcitonin, CRP, and LDH led to worse clinical outcomes. Our findings suggest that a thorough clinical and laboratory assessment of infected patients with cancer might help identify a more vulnerable population and implement more aggressive proactive strategies.

17.
JMIR Res Protoc ; 11(4): e34005, 2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35451973

RESUMEN

BACKGROUND: Mental health has come to be understood as not merely the absence of mental illness but also the presence of mental well-being, and recent interventions have sought to increase well-being in various populations. A population that deserves particular attention is that of health care workers, whose occupations entail high levels of stress, especially given the ongoing COVID-19 pandemic. A neuroscience-based web-based well-being program for health care workers-the Thrive program-has been newly developed to promote habits and activities that contribute to brain health and overall mental well-being. OBJECTIVE: This paper describes the protocol for a randomized controlled trial whose objective is to evaluate the Thrive program in comparison with an active control condition to measure whether the program is effective at increasing well-being and decreasing symptoms of psychological distress in health care workers at a designated Australian hospital. METHODS: The trial will comprise two groups (intervention vs active control) and 4 measurement occasions over a 12-week period. A survey will be administered in each of weeks 0, 4, 8, and 12, and the well-being program will be delivered in weeks 1-7 (via web-based video presentations or digital pamphlets). Each of the 4 surveys will comprise a range of questionnaires to measure well-being, psychological distress, and other key variables. The planned analyses will estimate group-by-time interaction effects to test the hypothesis that mental health will increase over time in the intervention condition relative to the active control condition. RESULTS: The Thrive program was delivered to a small number of wards at the hospital between February 2021 and July 2021, and it will be delivered to the remaining wards from October 2021 to December 2021. A power calculation has recommended a sample size of at least 200 participants in total. A linear mixed model will be used to estimate the interaction effects. CONCLUSIONS: This trial seeks to evaluate a new web-based well-being program for health care workers at a major public hospital. It will contribute to the growing body of research on mental well-being and ways to promote it. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621000027819; https://tinyurl.com/58wwjut9. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34005.

18.
J Clin Oncol ; 40(22): 2479-2490, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35394800

RESUMEN

PURPOSE: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: NCT02606461). RESULTS: Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION: Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.


Asunto(s)
Hidrazinas , Liposarcoma , Triazoles , Niño , Método Doble Ciego , Humanos , Hidrazinas/efectos adversos , Liposarcoma/tratamiento farmacológico , Liposarcoma/patología , Triazoles/efectos adversos
19.
J Natl Compr Canc Netw ; 20(2): 167-192, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35130500

RESUMEN

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.


Asunto(s)
Neoplasias Gástricas , Adenocarcinoma/patología , Humanos , Oncología Médica , Inestabilidad de Microsatélites , Calidad de Vida , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia
20.
J Surg Oncol ; 125(4): 560-563, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34820843

RESUMEN

COVID-19 has resulted in significant disruptions in cancer care. The Illinois Cancer Collaborative (ILCC), a statewide multidisciplinary cancer collaborative, has developed expert recommendations for triage and management of colorectal cancer when disruptions occur in usual care. Such recommendations would be applicable to future outbreaks of COVID-19 or other large-scale disruptions in cancer care.


Asunto(s)
COVID-19/prevención & control , Neoplasias Colorrectales/terapia , Atención a la Salud/normas , Terapia Combinada , Atención a la Salud/métodos , Atención a la Salud/organización & administración , Humanos , Illinois , Telemedicina/métodos , Telemedicina/organización & administración , Telemedicina/normas
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