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Cynthia S. E. Hendrikse MD Phyllis van der Ploeg MD PhD Nienke M. A. van de Kruis MD Jody H. C. Wilting MD Floor Oosterkamp BSc Pauline M. M. Theelen MSc Christianne A. R. Lok MD PhD Joanne A. de Hullu MD PhD Huberdina P. M. Smedts MD PhD M. Caroline Vos MD PhD Brenda M. Pijlman MD Loes F. S. Kooreman MD Johan Bulten MD PhD Marjolein H. F. M. Lentjes-Beer MD PhD Steven L. Bosch MD PhD Anja van de Stolpe MD PhD Sandrina Lambrechts MD PhD Ruud L. M. Bekkers MD PhD Jurgen M. J. Piek MD PhD 《Cancer》2023,129(9):1361-1371
Background
Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.Methods
Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.Results
Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.Conclusions
Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS. 相似文献23.
Steven P. Rowe MD PhD Martin G. Pomper MD PhD 《CA: a cancer journal for clinicians》2022,72(4):333-352
The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging—particularly when combined with liquid biopsy for screening purposes—promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology. 相似文献
24.
The use of radiation for primary liver cancers has historically been limited because of the risk of radiation-induced liver disease. Treatment fields have become more conformal because of several technical advances, and this has allowed for dose escalation. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is now able to safely treat liver tumors to ablative doses while sparing functional liver parenchyma by using highly conformal therapy. Several retrospective and small prospective studies have examined the use of SBRT for liver cancers; however, there is a lack of well-powered randomized studies to definitively guide management in these settings. Recent advances in systemic therapy for primary liver cancers have improved outcomes; however, the optimal selection criteria for SBRT as a local therapy remain unclear among other liver-directed options such as radiofrequency ablation, transarterial chemoembolization, and radioembolization. 相似文献
25.
Laura A. Huppert MD Ozge Gumusay MD Dame Idossa MD Hope S. Rugo MD 《CA: a cancer journal for clinicians》2023,73(5):480-515
Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data. 相似文献
26.
Diane Berish PhD Erica Husser PhD Jenny Knecht-Fredo MSN CRNP Jacqueline Sabol MEd George Garrow MD Judith Hupcey EdD CRNP FAAN Donna Fick RN GCNS-BC PhD FGSA FAAN 《Health services research》2023,58(Z1):78-88
Objective
To collaboratively implement the age-friendly health systems framework, known as the 4Ms: What Matters, Medication, Mentation, and Mobility, at The Primary Health Network (PHN), a federally qualified health center.Data Sources
Data were collected from PHN electronic medical records (EMRs) for individuals over age 65 from December 30, 2019 to December 24, 2021 and from Project ECHO© attendance and evaluation surveys.Study Design
The telementoring educational program, Project ECHO©, was used to engage PHN health care professionals working in rural areas of Pennsylvania to incorporate the 4Ms into their practice starting with the annual wellness visit (AWV). Project ECHO© was launched at three primary care sites. After 18 months, it was then disseminated to an additional 18 sites creating pilot and comparison groups. Outcomes included codesigned patient process metrics using EMR data and project ECHO© participant data.Data Collection Methods
EMR data were generated by system reports created by PHN's quality assurance program manager. Project ECHO© data were collected and managed using REDCap electronic data capture tools. Outcomes were aggregated, analyzed for trends over time, and compared between groups.Principal Findings
All nine process outcomes increased from baseline to follow-up at the three initial sites, ranging from 4% to 43% g. At year two, the three initial sites had higher rates on AWVs (pilot 24%, comparison 12%; p < 0.0001), Advance Care Planning (New on file, pilot 8%, comparison 2%; Discussed with patient, pilot 18%, comparison 13%; Patient declined, pilot 0%, comparison 0%; p = 0.0001), Dementia Screening (pilot 24%, comparison 12%; p < 0.0001), Fall Risk Management (pilot 43%, comparison 10%; p < 0.0001), and Mobility Goal (pilot 19%, comparison 9%; p < 0.0001); and lower rates on High-Risk Medication Elimination (pilot 54%, comparison, 63%, p < 0.02).Conclusions
Access to high-quality geriatric care for rural older adults can be improved by increasing health care professionals' knowledge of the 4Ms, beginning with its incorporation into the AWV. 相似文献27.
- DNA is the sequence that codes for proteins.
- Messenger RNA is transcribed from the DNA sequence of genes and translated into protein.
- It can be difficult to predict how a change in the DNA sequence will affect messenger RNA and protein quantity and quality.
- DNA translocation changes can cause the joining of sequences from two different genes or different parts of the same gene.
- DNA sequencing is often used clinically to predict how DNA changes might affect proteins.
- Alternatively, RNA sequencing can be used as a more direct measure of the effect of DNA changes on the protein products.
- This sequencing is important for identifying changes in cancer that may indicate response to targeted therapy, prognosis, or diagnosis.
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Marie V. Plaisime PhD MPH Marie Jipguep-Akhtar PhD Joseph J. Locascio PhD Harolyn M. E. Belcher MD MHS Rachel R. Hardeman PhD MPH Katherine Picho-Kiroga PhD Sylvia P. Perry PhD Sean M. Phelan PhD MPH Michelle van Ryn PhD LMFT MPH John F. Dovidio PhD 《Health services research》2023,58(Z2):229-237